These email address details are consistent with the previous findings that low levels of IgG3 may lead to the onset of complicated malaria while high IgG3 antibody levels may protect against malaria [25,26] and with the demonstration on the induction of CD40L stimulated na?ve B cells by IL4 alone or in combination with IL10 to express IgG1, IgG2 and IgG3, but little IgG4 [27]. em IL4 /em -590 counterparts. The different anti- em P. falciparum /em IgG1 and IgG3 levels among IL4 genotypes were observed. Complicated malaria patients with previous malaria experiences tended to have lower IgG3 levels in individuals carrying TT when compared to CT genotypes ( em P /em = 0.075). In contrast, complicated malaria patients without previous malaria experiences carrying CC NPS-1034 genotype had significantly higher anti- em P. falciparum /em IgG1 than those carrying either CT or TT genotypes ( em P /em = 0.004, em P /em = 0.002, respectively). Conclusion The results suggest that em IL4 /em -590C or T alleles participated differently in the regulation of anti-malarial antibody isotype profiles in primary and secondary malaria infection and, therefore, could play an important role in alteration of malaria severity. Background Anti- em Plasmodium falciparum /em specific antibodies play a critical role in immune protection against asexual blood stages of the parasite, in which anti- em P. falciparum /em IgG antibodies involved in reducing severity of the disease [1]. In particular, the cytophilic IgG1 and IgG3 subclasses are considered to protect against em P. falciparum /em , whereas IgG2 and IgM are not, and even suggested to block protective effects of the former Ig subclasses [2]. Anti- em P. falciparum /em IgE, as NPS-1034 well as total IgE antibodies, which are elevated in individuals exposed to malaria in Thailand, have been implicated to play a pathogenic role during malaria infection [1]. In contrast, the anti- em P. falciparum NPS-1034 /em IgE levels in asymptomatic individuals in Tanzania were associated with a reduced risk for subsequent malaria disease [3]. The regulation of antibody profiles in patients with complicated and uncomplicated malaria is still largely unknown. In both human and mice, different cytokines are thought to induce particular Ig isotypes. In humans, IL4 regulates B cells to express the 1, 2, 3, 4, 1, 2 and , germline gene transcripts (GLT) and to secrete the corresponding proteins [4-6]. IL10 promotes isotype switching from IgM to IgG1, IgG3, IgG4 and/or IgE [7-9] while IFN- promotes IgG2 [10,11]. The inter-individual variation in cytokine production may be reflected by polymorphisms in regulatory region of the corresponding genes. The em IL4 /em -590 C/T transition in em IL4 /em promoter was shown to influence the IL4 production as well as the elevated levels of total IgE [12,13]. The em IL4 /em -590T allele corresponded to em IL4 /em -524T and em IL4 /em -589T alleles in an alternative numbering scheme [14-16]. In the Fulani tribe in West Africa, em IL4 /em -524T allele was found to be associated with the elevated levels of anti- em P. falciparum /em IgG antibodies and protection against malaria [14], while em IL4 /em -589T allele was associated with the elevated levels of total IgE in children with severe malaria living in Burkina Faso [15]. Conversely, total IgE levels were significantly elevated in children with cerebral malaria who carried em IL4 /em -590T allele and have been living in Ghana [16]. Thus, the role of em IL4 /em -590T allele in regulating antibody profiles and malaria severity is controversial. In mice infected with em Plasmodium chabaudi chabaudi /em , the specific IgG2a and IgG3 antibodies are predominant in primary polyclonal B cell activation. At that point, IFN- is markedly stimulated, while IL4 is moderately enhanced. In secondary IgG1-restricted response, NPS-1034 only IL4 is produced [17]. According to previous findings, the em IL4 /em -590 LDH-B antibody C/T polymorphism influences the balance between IL4 and IFN- and thus, could alter the severity of malaria [18]. When the same sets of sera were used subsequently to determine the anti- em P. falciparum /em IgG subclasses and.