2A). However, the number of antigen-specific cells recovered at day 5 was not different between CpG-treated and control mice. Co-injection

of poly(I:C), LPS, or imiquimod did not modify the number of tetramer+ cells recovered from the spleens or LN at these early time points compared with mice immunized with peptide alone (data not shown), demonstrating a selective potency of CpG to enhance the early expansion of CD8+ T cells in response to soluble peptide in vivo. Consistent with the increased clonal population size at day 3 post-immunization, tetramer+ cells recovered from mice treated with CpG displayed a more robust proliferation profile compared with control mice that received peptide alone, as indicated by CFSE dilution (Fig. 2B). The effects of CpG were not as striking LY294002 in vitro in the spleen, though similar trends were observed. By day 5, however, there was no accumulation of CFSElo cells regardless of CpG treatment, with proliferation profiles similar to those observed previously at day 5 in all groups (data not shown). Further, the numbers of tetramer+ cells recovered from the spleens of immunized mice 10 days post-immunization were

not changed by treatment with any TLR, including CpG (Fig. 2C). Thus, in spite of inducing more robust early proliferative activity, CpG treatment could not modify the widespread cell death observed after peptide immunization. Addition of MHC class II-restricted peptides to the R788 inoculum to elicit help from CD4+ T cells did not enhance the survival of the peptide-stimulated CD8+ T cells, even in the presence of CpG (Supporting Information Fig. 2). In mice that were immunized with peptide alone, we could not detect antigen-specific T cells by ELISPOT, suggesting that they were unable

to produce IFN-γ (Fig. 2D). However, antigen-specific ifenprodil cells from the dLN of mice treated with CpG and peptide were readily detected by IFN-γ ELISPOT. These differences were not merely due to differences in frequency, as there was a ten-fold increase in tetramer+ cells measured by FACS, but there were greater than 300-fold differences in the number of IFN-γ-producing cells. Curiously, antigen-specific IFN-γ secreting T cells were not detected in the spleen when immunizing mice with either peptide alone or CpG with peptide. CpG clearly modulates the CD8+ T-cell response to soluble peptide by promoting cell division and clonal expansion, as well as supporting IFN-γ production. However, CpG could not induce T-cell survival, as there was no significant increase in the final magnitude of the CD8+ T cell after the contraction phase. Since CpG has been shown to have many effects on the immune system 21 that may change over time, we modified the timing of the CpG administration relative to the peptide to investigate whether there were temporal effects of the CpG that could enhance T-cell survival.

This magnitude of change is similar to that seen in the trial by Fishbane et al. from 2009.109 Agarwal et al. have also published similar findings, albeit with less robust

data. Using a composite of three previous studies, they found that paricalcitol use was associated with a significant reduction in spot dipstick urine quantification, which was independent of changes in PTH level, ACE inhibitors or angiotensin Seliciclib nmr II receptor blockers,110 and in an a dose-finding trial Alborzi et al. showed that albuminuria could be reduced by almost 50% compared with pretreatment, and the reduction in urinary loss was not dose dependent (paricalcitol).76 In an uncontrolled open-label trial Szeto’s group used oral 1,25-OHD 1 µg/week for 1 week and had similar efficacious results, with reductions in urinary protein: creatinine ratio (PCR) from 1.98 ± 0.74

to 1.48 ± 0.81 g/g (P < 0.004).111 There is increasing recognition of the important LBH589 cell line role of the cardiac microcirculation in the aetiology of cardiac disease in patients with CKD. Cardiac myocyte hypertrophy is associated with capillary : myocyte mismatch, resulting in ischaemic tissue, fibrosis and scarring; a process that may underlie the increased rate of sudden cardiac death in CKD populations.112 Using 1,25-OHD 6 ng/kg/day for 12 weeks in subtotal nephrectomized rats, Koleganova’s group demonstrated that Vascular Endothelial Growth Factor (VEGF) receptor (type II) significantly upregulated in cardiac Mephenoxalone tissue, although VEGF concentrations were not significantly altered.113 1,25-OHD treated rats demonstrated less expansion of the cardiac

interstitium and fibrosis, increased capillary length-density and decreased mean intercapillary distance compared with controls.113 Thus, it may be that vitamin D can increase the efficacy of available VEGF by receptor upregulation thereby ameliorating capillary : myocyte mismatch. Unfortunately, given the nature of the pathophysiology, and the difficulty of assessing this in vivo, there are currently no trials to support this hypothesis in humans. Vitamin D has been implicated in atherogenesis. Rahmen et al. demonstrated that decreased VDR stimulation resulted in over-expression of MMP-2 and -9 (which are responsible for vascular wall remodelling, type I collagen deposition and plaque destabilization, rupture and thrombosis114) and downregulation of Tissue Inhibitors of MMPs (TIMPs-1 and -3).115 In contrast, 1,25-OHD use resulted in reduced endothelial binding and pro-inflammatory activity of NFκB,116 decreased production of prothrombotic mediators,117 and diminished thrombogenesis and platelet aggregation as a result of thrombomodulin upregulation and Plasminogen activator-inhibitor I (PAI-1) downregulation.118 As yet, little in vivo work exists in this area.

This review discusses the key signalling complexes regulating integrin activation and function in both ‘inside-out’ and ‘outside-in’ pathways in T lymphocytes, including kinases, SLP-76, DZNeP manufacturer VAV1, ADAP, SKAP-55, RapL, RIAM, Rap1, Talin and Kindlin. Integrins are transmembrane adhesion receptors that mediate cell–cell and cell–extracellular matrix adhesion and also induce bidirectional signalling across the cell membrane to regulate

cell proliferation, activation, migration and homeostasis.1 Each integrin contains one α subunit and one β subunit. So far, eighteen α subunits and eight β subunits have been characterized that form 24 different integrins in vertebrates. Studies from gene knockout mice lacking different α and β subunits have indicated that various integrins play crucial roles during development of different organs. α5 knockout mice show vascular defects, and α4 knockout mice have impaired cardiac development.2,3α3 knockout mice are perinatally lethal with marked abnormalities in lung development and α6 knockout mice develop severe

skin blistering.4,5 Except for their crucial role in organ development, integrins participate in OTX015 the process of wound healing, cancer, immune responses against infection and autoimmune diseases. At least 12 integrins are expressed in various types of leucocytes and platelets (Table 1).6 Accumulation of evidence from human and mouse models has shown that defects in integrin expression or activation in these immune cells result in serious immunodeficiency or autoimmune

diseases. Mice with null mutations of the αL or β2 subunit show phenotypes similar to patients with leucocyte adhesion deficiency I, including spontaneous infections, impaired leucocyte adhesion and migration to the inflamed and infected Roflumilast skin.7 In this context, integrins have served as potential therapeutic targets for diseases, such as blocking antibodies to very late antigen-4 (α4β1) (i.e. natalizumab) and leucocyte function-associated antigen-1 (LFA-1; αLβ2; or CD11a CD18) (i.e. efalizumab) in the treatment of multiple sclerosis and psoriasis, respectively.8,9 In the past decades, numerous studies have emerged to propose models of integrin activation and have identified key effectors that could regulate integrin activation. These studies might provide new target molecules to treat patients with these immune cell-based disorders. Integrin conformational changes are thought to convert integrin affinity from low or intermediate levels to high levels. As a transmembrane receptor, the extracellular parts of α and β subunits form a ligand-binding headpiece and the transmembrane parts are followed by short cytoplasmic tails. In a resting state, the ligand-binding headpiece of an integrin is bent and close to the cell membrane, whereas the cytoplasmic tails are close together to form a conformation with low affinity.

Results:  We observed that S1P stimulates migration of HDMECs concomitant with upregulation of CTGF/CCN2 expression. Furthermore, the blockade of endogenous CTGF/CCN2 via siRNA abrogated S1P-induced HDMEC migration and capillary-like tube formation. Full-length CTGF induced cell migration and capillary-like tube formation with a potency similar to that of S1P, while C-terminal

domain of CTGF was slightly less effective. However, N-terminal domain had only a residual activity in inducing capillary-like tube formation. Conclusions:  This study revealed that CTGF/CCN2 is required for the S1P-induced endothelial cell migration, which suggests that CTGF/CCN2 may be an important mediator of S1P-induced physiological and pathological angiogenesis. Moreover, this study shows that the pro-migratory activity of CTGF/CCN2 is located in the C-terminal domain. “
“Please cite this paper as: Ritter, selleckchem Davidson, Henry, Davis-Gorman, Morrison, Frye, Cohen, Chandler, McDonagh and Funk (2011). Exaggerated Neutrophil-Mediated Reperfusion Injury after Ischemic Stroke in a Rodent Model of Type 2 Diabetes. Microcirculation 18(7), Selleckchem GDC973 552–561. Objective:  We tested the hypothesis that both chronic and acute inflammatory

processes contribute to worse reperfusion injury and stroke outcome in an experimental model of T2DM. Materials and Methods:  Twelve- to thirteen-week-old male Zucker Diabetic Fatty (ZDF) rats vs. Zucker Lean Controls (ZLC) rats were tested at baseline and after middle cerebral artery occlusion Phospholipase D1 (ischemia) and reperfusion

(I–R). Neutrophil adhesion to the cerebral microcirculation, neutrophil expression of CD11b, infarction size, edema, neurologic function, sICAM, and cerebral expression of neutrophil–endothelial inflammatory genes were measured. Results:  At baseline, CD11b and sICAM were significantly increased in ZDF vs. ZLC animals (p < 0.05). After I–R, significantly more neutrophil adhesion and cell aggregates were observed in ZDF vs. ZLC (p < 0.05); infarction size, edema, and neurologic function were significantly worse in ZDF vs. ZLC (p < 0.05). CD11b and sICAM-1 remained significantly increased in ZDFs (p < 0.05), and cerebral expression of IL-1β, GRO/KC, E-selectin, and sICAM were significantly induced in ZDF, but not ZLC groups (p < 0.05) after 2.5 hours of reperfusion. Conclusion:  Both sides of the neutrophil–endothelial interface appear to be primed prior to I–R, and remain significantly more activated during I–R in an experimental model of T2DM. Consequently, reperfusion injury appears to play a significant role in poor stroke outcome in T2DM. "
“Please cite this paper as: Shi VY, Bao L, Chan LS. Inflammation-driven dermal lymphangiogenesis in atopic dermatitis is associated with CD11b+ macrophage recruitment and VEGF-C up-regulation in the IL-4-transgenic mouse model. Microcirculation 19: 567–579, 2012.

Table 1 lists some of these interventions. Susceptibility

to AN is strain-specific, with BALB/c mice being highly sensitive,23 while C57BL/6 mice are highly resistant to renal injury.11 Breeding experiments have identified a single gene locus with recessive inheritance on chromosome 16 that confers susceptibility to AN. Susceptibility alleles at this locus are associated with blunted expression of protein arginine methyltransferase on chromosome 8, a protein implicated in cellular sensitivity to chemotherapeutic agents.56 LY2157299 Additionally, genetic background influences severity of AN. In these same studies a locus on chromosome 8 has been identified that influences the severity and progression of nephropathy. Lymphocyte number is a determinant of sensitivity to Adriamycin-induced renal injury. Compared with wild-type BALB/c mice, SCID BALB/c require only half the dose

of Adriamycin to induce disease10 However, Adriamycin does not cause renal injury in lymphocyte-depleted recombinase activating gene-1 knockout C57BL/6 mice (V. Lee, unpubl. obs., 2010) meaning that lymphocyte number alone does not explain the resistance of C57BL/6 mice to Adriamycin-induced renal injury. Susceptibility Vismodegib datasheet to Adriamycin is likely to lie in the immunological differences between species, for example, as occurs with BALB/c and C57BL/6 mice. It is convenient to use the Th1/Th2 paradigm to summarize the differences. C57BL/6 mice have immune responses that are, in general, polarized towards the Th1 axis whereas Glutamate dehydrogenase BALB/c mice possess immune responses that deviate towards the Th2 type. Therefore, the immune system of C57BL/6 mice is better equipped against and hence less susceptible to intracellular infection (e.g.

Listeria57) but is more susceptible to antibody-mediated autoimmune disease such as myasthenia gravis. The immune response of C57BL/6 mice, as compared with BALB/c mice, is characterized by greater amounts of Th1 cytokines such as IL-12 and IFN-γ and less Th2 cytokines such as IL-4. The Th1 response is also characterized by upregulation of dendritic cells to a more mature phenotype. Consistent with this hypothesis, a recent study has shown that CD4+CD25− T cells isolated from C57BL/6 mice are less susceptible to suppression by CD4+CD25+ Tregs than their BALB/c counterparts, and that C57BL/6 mice possess fewer CD4+CD25+ Tregs than BALB/c mice.58 Therefore, a possible explanation for the relative resistance of C57BL/6 mice to Adriamycin-induced renal injury may be that Th1-immune responses are protective against AN, whereas Th2 responses are not. Zheng and colleagues59 have recently reviewed susceptibilities of mice to AN (Table 2) supporting the variability in response to Adriamycin across strains. Adriamycin induces injury by direct toxic damage to the glomerulus with subsequent tubulointerstitial injury.

cruzi infected mice, and IL-12 + IL-18-treated

mice. Data using specific inhibitors of MCP-1 and CCR2 further confirm this hypothesis. Interestingly, our data support the fact that IL-12 and IL-18 are the cytokines responsible for MCP-1 upregulation in the thymus, since we observed that in vitro recombinant IL-12 and IL-18 are able to significantly increase MCP-1 only in thymocytes from IL-12 + IL-18-cDNA treated mice, indicating that cells present in the thymi of mice exposed to systemic IL-12 + IL-18 but not in normal mice contain cells with the ability to produce this chemokine. Accordingly, further analysis demonstrates that thymic B cells and T cells CD44lo are the main producers of this chemokine in the thymus under these inflammatory conditions. Based on the data presented in this work, we propose a novel concept of peripheral lymphocyte Tyrosine Kinase Inhibitor Library recirculation during nonphysiological conditions. We demonstrate that in any potential situation where large amounts of IL-12

and IL-18 are produced Dinaciclib chemical structure as a consequence of an infectious/inflammatory process, the thymus cell number is reduced favoring the creation of new niches in this organ that facilitate peripheral B and T cells entrance to the thymus. Interestingly, this phenomenon occurs in the absence of any antigenic stimulation and seems to be part of bystander activation of certain peripheral mature B and T cells. The fact that systemic IL-12 and IL-18 expression is observed in numerous situations opens the possibility that this migratory events described here are also possible in a numerous type of pathological processes. At the present moment, 4-Aminobutyrate aminotransferase we are evaluating if the entrance of B and T cells is due to a mere opportunism of cells during a moment of large expansion of leukocytes or if it is a coordinated process that plays a role in thymus physiology. Moreover, evaluation of peripheral cell localization in the thymus could provide important information not only about the source of required factors peripheral B and T cells use to survive in the thymus but also about the role they

might have in different thymic processes such as negative and positive selection and differentiation of immature cells in this organ. Female or male C57BL/6 (B6) and OT-I mice (Jackson Laboratory) used in this study were 6–10 week old and were maintained under specific pathogen-free conditions. The experimental protocols were approved by the Institutional Animal Care and Use Committee (IACUC). Our animal facility obtained NIH animal welfare assurance (assurance number A5802-01, OLAW, NIH, USA). B6 mice were injected i.p. with LPS (055-B5, Sigma) in a sublethal concentration of 20 μg per mouse in 200 μL PBS once a day for 3 consecutive days. Trypanosoma cruzi trypomastigotes were maintained by serial passages in B6 mice. B6 mice were i.p. infected with 5 × 105 trypomastigotes from T. cruzi diluted in PBS.

“
“To assess whether interleukin (IL)-1beta, IL-18 and interleukin-1 converting enzyme (ICE) are involved in the pathogenesis of endometriosis. Peritoneal fluid (PF) was obtained from 85 women with and without endometriosis.

Peritoneal macrophages were cultured and the culture media collected. IL-1beta, IL-18 and ICE levels were measured by the enzyme-linked immunosorbent assay (ELISA). Levels of IL-1beta and ICE in PF of women with endometriosis were higher than those in the control group. However, PF level of IL-18 was significantly lower in the study group than in the controls. Higher secretion of IL-1beta by peritoneal macrophages and lower IL-18 and ICE in endometriosis patients than in control selleckchem were observed. Following lipopolysaccharide (LPS) stimulation, the macrophages secreted more IL-1beta, IL-18 and ICE in all groups. The results pointed to impairment

of the secretion of the IL-1 cytokine family in endometriosis. Invalid IL-1beta and IL-18 maturation by ICE may be an important pathogenic factor GSI-IX in vivo in endometriosis. “
“Neutrophils potently kill tumour cells in the presence of anti-tumour antibodies in vitro. However, for in vivo targeting, the neutrophils need to extravasate from the circulation by passing through endothelial barriers. To study neutrophil migration in the presence of endothelial cells in vitro, we established a three-dimensional collagen culture in which SK-BR-3 tumour colonies were grown in the presence or absence of an endothelial barrier. We demonstrated that — in contrast to targeting FcγR on neutrophils with mAbs — targeting the immunoglobulin A Fc receptor (FcαRI) instead triggered Dapagliflozin neutrophil migration and degranulation leading to tumour destruction, which coincided with release of the pro-inflammatory cytokines interleukin (IL)-1β and tumour necrosis factor (TNF)-α. Interestingly, neutrophil migration was enhanced in the presence of endothelial cells, which coincided with production of significant levels of the neutrophil chemokine IL-8. This supports the idea that stimulation of neutrophil FcαRI, but not

FcγR, initiates cross-talk between neutrophils and endothelial cells, leading to enhanced neutrophil migration towards tumour colonies and subsequent tumour killing. Neutrophils represent the most populous type of cytotoxic effector cells within the blood and their numbers can easily be increased by treatment with granulocyte colony-stimulating factor (G-CSF) [1]. Because depletion of these cells resulted in increased tumour outgrowth in animal models, neutrophils may play a role in tumour rejection in vivo [2-4]. It is also becoming increasingly clear that neutrophils secrete a plethora of cytokines and chemokines that can attract other immune cells, such as monocytes, dendritic cells and T cells [5], which may result in more generalised anti-tumour immune responses.

3 cmH2O as a result of increased

intra-abdominal pressure, which is necessary for emptying the neobladder. In the present study, the mean maximum voiding pouch pressure (above baseline) was 84.4 ± 46.4 and 81.4 ± 37.8 cmH2O, respectively. However Porru[13] reported higher neobladder pressure at Qmax (140 cmH2O). One limitation in comparing the pressure values among various studies is the definition of “voiding pressures” which could be either equivalent to Pves or Pdet. Urethral length and function has been evaluated more extensively selleck screening library in patients undergoing radical prostatectomy (RP) for prostate cancer. Recent data from Memorial Sloan Kettering Cancer Center suggests that urethral length (on magnetic resonance imaging) after surgery as well as percentage loss of the length due to surgery corroborate with status of continence in men undergoing RP.[33] Similarly, others have reported an inverse correlation between functional urethral length and MUCP, and incontinence.[16] Sphincter/urethral function have been reported with UPP measurement in patients with orthotopic neobladder.[13, 19, 21, 24] Koraitim et al.[19] studied cystometric and urethrometric urodynamic parameters in 88 patients having undergone ONB. They studied a total 28

parameters, out of which MUCP correlated with both diurnal and nocturnal incontinence, and resting pouch pressure with nocturnal incontinence. However, absolute values of none of the parameters were mentioned. In a series of 12 men Porru and Usai[13] noted two PLX-4720 order patients had reduced urethral pressure (MUCP < 45 cm H2O). The incidence of nocturnal incontinence was 56%; they reported only descriptive association between incontinence, and MUCP and pouch pressure. El Bahnasawy et al.[21] found RVX-208 a significant difference in MUCP between continent and incontinent groups. We have found a correlation between lower FUL and incontinence;

however, none with MUCP. The strength of the present study is tabulation of all relevant UDS parameters for ready reference, despite the limitation of small samples. The effect of pelvic floor strengthening and relaxation exercises have been advised in such patients by most experts in the field. However, an objective urodynamic correlation of the effect of these exercises has not been reported. With the limitation of small sample size and short follow-up we tried to elucidate the effects of these exercises on voiding function. There was a trend of increase in Qmax with more pronounced decrease in EMG activity and less pronounced abdominal pressure with the exercises (Fig. 3). Ureteroileal anastomotic stenosis with upper tract deterioration was significantly higher in patients with antirefluxing compared with those with refluxing anastomosis (13.5% vs 3%).[34, 35] Abol-Enein and Ghoneim described serous-lined extramural ureteral reimplantation[9, 10] and reported reflux in 3% of patients and deterioration of renal function in 4%.

Nitric oxide has a wide variety of regulatory activities, which can affect the chronic host response to infection [2-5]. In the case JNK inhibitor of Mycobacterium avium, the bacteria are not susceptible to the toxic effects of nitric oxide [6], allowing us to probe the role of reactive nitrogen intermediates in regulation of the T-cell response to mycobacterial infection

without the confounding factor of uncontrolled bacterial growth. Nitric oxide acts on physiological systems with effects dependent upon concentration, the relative levels of reactive oxygen radicals and pH [7]. At low concentrations, nitric oxide acts as a signaling molecule, either in a cGMP-dependent or -independent manner, to promote vascular integrity, mediate neurotransmission, and regulate cellular respiration by altering the affinity of cytochrome C for oxygen [7, 8]. At high concentrations, nitric oxide inhibits respiration and causes nitrosative damage MK-1775 molecular weight to proteins, lipid peroxidation, and DNA [9, 10]. The balance between nitric oxide and oxygen radicals is important, as nitric oxide can reduce oxidative stress [11] but also generates peroxynitrite, which is itself damaging [12]. The damage generated by high levels of nitric oxide is detrimental to cells and results in apoptosis [9]. The impact of nitric oxide on the immune response has been extensively analyzed with identification of both positive and negative regulatory roles [13].

In humans, nitric oxide limits IL-2 release and proliferation of T cells via activation of the cGMP-dependent protein kinase, cGK I [14]. In Trypanosoma brucei mouse models, nitric oxide inhibits the accumulation of IL-2- and IFN-γ-producing T cells [15]. In both an in vitro system [16] and a Listeria monocytogenes mouse model [17], the inhibition of nitric oxide synthase (Nos)

results in improved antigen-specific T-cell responses. Nitric oxide also acts as an anti-inflammatory agent by limiting the interaction of leucocytes with the endothelial monolayer [18]. Nitric oxide can drive IL-10-producing regulatory T cells, limit the expansion of Th17 cells [19, 20], and regulate the IL-12 pathway both positively [21] and negatively [22]. Indeed, at low levels, it can augment the generation of Th1 cells by increasing expression of IL-12Rβ2 [23, 24] Liothyronine Sodium and augment IFN-γ−mediated signaling [25]. In mycobacterial disease, nitric oxide is essential for the control of Mycobacterium tuberculosis but dispensable for the control of M. avium [4]. It limits the accumulation of activated T cells in the Mycobacterium bovis BCG model [26], the M. tuberculosis model [27], and the M. avium model [6] with an increased IFN-γ response being seen in both M. avium [6] and M. tuberculosis infected nos2−/− mice [28]. Absence of nitric oxide in M. avium infection results in lesions with increased cellularity and collagen deposition [6, 29, 30].

While we found no evidence for an association between parasite carriage by microscopy or PCR and concurrent antibody prevalence or titre in study participants

aged 6 years and older (data not shown), parasite carriage was associated with elevated antibody prevalence and titre in younger children. When parasite carriage among 1- to 5-year-old children was categorized as parasite-free, submicroscopic infection or patent (microscopically detectable) infection, antibody prevalence Antiinfection Compound Library increased across these categories for AMA-1 (P < 0·001), MSP-119 (P = 0·006) and MSP-2 (P < 0·001), but not CSP (P = 0·77). Antibody titre increased across these categories of parasite carriage for AMA-1, MSP-119, MSP-2 and CSP (Figure 3; P = 0·001). Anti-gSG6 antibody prevalence and titre also increased across these categories (P < 0·001). Pairwise comparisons are presented in Table 2. We further explored the dynamics of antibody titres

in relation to malaria infections in children 1–5 years of age (i) who were consistently parasite-positive throughout the study; (ii) who were parasite-free throughout the study; (iii) who were parasite-positive at enrolment but did not become re-infected after treatment; and (iv) who were parasite-free at enrolment but acquired an infection during follow-up. Children below 5 years of age who were consistently parasite-positive during the study did not have consistently higher titres of see more antibodies against AMA-1 (P = 0·21), MSP-119 (P = 0·26), MSP-2 (P = 0·91), CSP (P = 0·29) or gSG6 (P = 0·23) compared with children who were consistently parasite-negative (Figure 4; Table 3). However, the dynamics of antibody titres were influenced by parasite exposure during the study. In children of this age group who were consistently parasite-positive, antibody titre against AMA-1 (P = 0·39), MSP-119 (P = 0·47), MSP-2 (P = 0·48) and gSG6 (P = 0·25) did before not change significantly with time, while antibody titres for CSP showed a statistically significant decrease (P = 0·011). In contrast, we found evidence for

a decline in antibody titres for AMA-1 (P < 0·0001), MSP-119 (P = 0·015), CSP (P = 0·016) and gSG6 (P = 0·0005) with a borderline significant trend for MSP-2 (P = 0·08) for children of this age group who were never parasite-positive by microscopy or PCR during the study. Similarly, antibody titres decreased in children who were parasite-positive at enrolment but did not become re-infected after treatment for AMA-1 (P < 0·0001), MSP-119 (P = 0·003), MSP-2 (P = 0·0001), CSP (P < 0·0001) and gSG6 (P < 0·0001). Children who acquired an infection during the study showed no consistent patterns in antibody titres: antibody titres for all antigens were stable or elevated 6 weeks after enrolment in children aged 1–5 years, with a decline between weeks 6 and 16 to (below) enrolment levels.