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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This review describes the role of cytokines produced by CD4+ T cells and macrophages in response to the erythrocytic stages of P. chabaudi chabaudi and other malaria infections in mice. Since virtually all compartments of the immune system are activated during the response against malaria, the variety of cytokines produced during infection is considerable. There is, however, a clear differential expression of different cytokines during primary infection. Th1-related cytokines are predominantly produced during the acute phase of infection, and lead mainly to the induction of macrophage-derived cytokines. This antibody-independent pathway is probably on the one hand, sufficient for parasite control early in infection via macrophage-associated inflammatory responses, but can, on the other hand, also lead to the pathological consequences of infection. As the infection progresses, the pattern of cytokine production shifts towards a Th2-like response. B cells play a crucial role in this process. A major consequence of this switch to a production of Th2-related cytokines later in infection would be the down-regulation of IFN-gamma-induced macrophage activation and the promotion of antibody production by mature B cells. This suggest that the mechanism of parasite control in the later stages of infection is predominantly antibody-dependent.
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PMID:The roles of cytokines produced in the immune response to the erythrocytic stages of mouse malarias. 812 18

Crude merozoite antigens from P. falciparum were used to analyse the proliferative response of peripheral blood mononuclear cells from 114 inhabitants of the village of Dielmo (Senegal, West Africa), who are exposed continuously to malaria transmission. The high or low responses to merozoite antigens obtained in lymphocyte stimulation assays were correlated to the presence or absence of parasites, to the IFN-gamma production and to the HLA-phenotype. High responders produced high levels of IFN-gamma while low responders did not secrete IFN-gamma (23/27). The two HLA phenotypes HLA-B51 and HLA-DR1 were significantly associated with high response (p < 0.05).
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PMID:Lymphocyte response in vitro to Plasmodium falciparum merozoite antigens in donors from a holoendemic area. 823 8

Crude merozoite antigens from Plasmodium falciparum were used to evaluate the proliferative response of peripheral mononuclear cells (PBMCs) from 114 inhabitants of the village of Dielmo (Senegal, West Africa) exposed continuously to malaria transmission. The high or low responses to merozoite antigens obtained in lymphocyte stimulation assays were correlated with the presence or absence of parasites, IFN-gamma production and HLA phenotype. The high responders produced high levels of IFN-gamma, in contrast to the low responders, most of whom did not secrete IFN-gamma (23/27). Among others, the two HLA phenotypes HLA-B51 and HLA-DR1 were significantly associated with a high response (P < 0.05).
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PMID:Lymphocyte response in vitro to Plasmodium falciparum merozoite antigens in donors from a holoendemic area. 829 98

Mice infected with Plasmodium berghei K173-parasitized erythrocytes develop severe hypothermia followed by death as a consequence of murine cerebral malaria early in the second week after infection. A single intraperitoneal injection of 10(5) Units of IFN-gamma given between Day 4 and Day 6 postinfection results in a transient decrease of body temperature. No effect on parasitemia and cerebral malaria is obtained by this treatment. Daily injections of relatively low doses of IFN-gamma delays the patency of the infection for 2 days. Furthermore the proliferation rate of the parasites is reduced and the development of cerebral malaria is also delayed for 2 days. The reduction of body temperature, as found in untreated infected mice, is absent. Administration of IFN-gamma by means of a continuous delivery from intraperitoneally inserted osmotic pumps (1.2 x 10(4) Units of IFN-gamma/24 hr) also delays patency and inhibits parasitemia. Body temperature decreases during infection but mice are protected against the development of cerebral malaria. In nude mice, this treatment inhibits parasitemia to the same extent. However, reduction of body temperature was also prevented. High doses of IFN-gamma delivered by osmotic pumps (2.5 x 10(4) or 10(5) Units of IFN-gamma/24 hr) appear to be lethally toxic in conventional as well as in nude mice, independently of infection. Cerebral malaria-like symptoms are found in these mice. Treatment of infected C57BL/6J mice with antibody to IFN-gamma 4 days before and after infection as well as on the day of infection enhances parasitemia but does not affect the development of murine cerebral malaria. Single injections of anti-IFN-gamma-antibody 6 hr prior to infection or 7 days after infection have no effect. In CBA/Ca mice, treatment with anti-IFN-gamma-antibody enhances parasitemia; furthermore protection against cerebral malaria was obtained in part of the mice.
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PMID:Plasmodium berghei: recombinant interferon-gamma and the development of parasitemia and cerebral lesions in malaria-infected mice. 837 90

Infection with Plasmodium berghei ANKA (PbA) leads, in susceptible strains of mice, to the development of cerebral malaria (CM), a lethal syndrome that reproduces some features of human CM. To study a possible relationship between genetic susceptibility to CM and the cytokine expression pattern, we quantitatively evaluated gene expression on RNA extracted from various organs of malaria-infected mice, using strains that are susceptible and resistant to CM. Northern blot analysis and semi-quantitative PCR showed that CM is associated with an increased TNF-alpha mRNA accumulation in the brain of mice developing the neurologic complications of CM. An increased IFN-gamma mRNA accumulation and a decreased expression of IL-4 and TGF-beta genes were also observed in mice susceptible to CM. In vitro restimulation studies using crude malarial Ag showed that lymphoid cell proliferation was higher in CM-susceptible than in CM-resistant infected mice. Moreover, susceptible mice produced large amounts of IFN-gamma, in a dose-dependent manner, in response to PbA Ag, whereas cells from resistant mice failed to produce significant amounts of this cytokine. Conversely, IL-2 and IL-4 production was significantly higher in infected CM-resistant mouse cells. No difference was seen in the production of IL-3 and IL-5 between resistant and susceptible PbA-infected mice. Upon stimulation with various malarial Ag, comparable amounts of TNF-alpha were produced by macrophages of either strain of mice. Taken together, these findings indicate that susceptibility to CM resides at the level of T cells rather than macrophages. Furthermore, the cytokine production profile is consistent with a predominant Th1-like response in mice developing cerebral complications of malaria.
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PMID:Profiles of cytokine production in relation with susceptibility to cerebral malaria. 840 39

Recombinant rat interferon-gamma (rrIFN-gamma) was tested for its antimalarial activity in three different models of Plasmodium chabaudi-blood stage malaria. Doses ranging from 1 x 10(4) to 1 x 10(5) U of rrIFN-gamma were used in each model. In BALB/c mice (lethal infection), prophylactic treatment with daily intraperitoneal (i.p.) injections reduced parasitemia and delayed mortality. In contrast, subcutaneous administration of rrIFN-gamma was inefficient, as was curative schedule of i.p. administration. Euthymic Fischer rats, which develop an acute and resolutive infection, were partly protected by i.p. prophylactic administration of rrIFN-gamma. Parasitemia was reduced without being lengthened, resulting in a marked decrease in parasite burden. Subcutaneous administration was less efficient whereas curative schedule was not. Athymic (nude) Fischer rats which present a longlasting and stable infection were treated with prophylactic and curative schedules of i.p. administration of rrIFN-gamma. In each case, rrIFN-gamma-treated nude rats, as control nude rats, were unable to resolve their chronic infection. The conditions required to obtain a beneficial effect are thus restrictive for a therapeutic use in humans. Moreover, these results show that, despite the fact that IFN-gamma is considered as a major component of the immune response, this cytokine alone is not sufficient to induce the totality of the effector mechanisms necessary to cure malarial infections.
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PMID:IFN-gamma treatment of rodents infected with erythrocytic stages of Plasmodium chabaudi: differential effects according to the immunological status. 850 41

Spleen and lymph node cells from Plasmodium yoelii 17X-infected, C57BL/6 (B6), and DBA/2 (D2) mice were cultured in vitro with parasite antigens. The ability of these cells to proliferate was quantified by uptake of [3H]thymidine and ELISA was used to measure secretion of IFN-gamma and IL-5. B6 mice are relatively susceptible to P. yoelii 17X infection compared to D2 mice. Susceptible mouse strains develop higher levels of parasitemia, become more anemic, and take longer to resolve their infections than do resistant strains. Following splenectomy, D2 mice resisted P. yoelii 17X infections as well as did sham-operated controls, but splenectomized B6 mice failed to resolve their infections and all died. Spleen cells from infected mice of either strain were activated in vitro as evidenced by their proliferation in the absence of exogenous antigen. When malaria antigen was added to these cultures, cells from resistant D2 mice responded strongly with increased proliferation, whereas cells from susceptible B6 mice responded weakly, and on Day 14 postinfection, responses were actually suppressed. Mesenteric lymph node cells from infected B6 and D2 mice did not proliferate in the presence or absence of P. yoelii 17X antigen unless the spleen was removed. Following splenectomy, mesenteric lymph node cells from D2 mice, but not B6 mice, proliferated strongly compared to cells from sham-operated controls. IFN-gamma and IL-5 production from spleen and lymph node cells was measured following in vitro stimulation with P. yoelii 17X antigen. Spleen cells from D2 mice produced levels of IFN-gamma increased over those of cells from B6 mice.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasmodium yoelii: cellular immune responses in splenectomized and normal mice. 851 76

We investigated the kinetics of tissue-specific mRNA expression and systemic production of tumor necrosis factor alpha (TNF-alpha) and the kinetics of splenic expression of mRNAs of gamma interferon (INF-gamma) and interleukin-4 (IL-4), cytokines that may regulate TNF-alpha production, during the early phase of blood-stage infection with Plasmodium chabaudi AS. Northern blot analysis revealed that resistant C57BL/6 mice, which clear the infection by 4 weeks, had higher levels of TNF-alpha mRNA in the spleen and liver early during infection that did susceptible A/J mice, which succumb to the disease 10 days after initiation of infection. Treatment of resistant mice with a polyclonal anti-TNF-alpha antibody confirmed the protective role of TNF-alpha early during the course of infection. Furthermore, resistant C57BL/6 mice also expressed high levels of mRNA of IFN-gamma (a Th1 marker) and low levels of mRNA of IL-4 (a Th2 marker) in the spleen, whereas susceptible A/J mice had low levels of IFN-gamma mRNA but high levels of TNF-alpha mRNA in the liver and had high levels of TNF-alpha protein in serum, as measured by enzyme-linked immunosorbent assay, later during infection just before death occurred. These results demonstrate that a Th1-associated increase in TNF-alpha mRNA expression in the spleen early during infection correlates with resistance to P. chabaudi AS, whereas increased TNF-alpha mRNA levels in the liver and excessive levels of the TNF-alpha protein in serum later during infection correlate with susceptibility. Thus, the role of the TNF-alpha during malaria appears to depend on the timing and site of its expression and the presence of cytokines regulating its production.
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PMID:A Th1-associated increase in tumor necrosis factor alpha expression in the spleen correlates with resistance to blood-stage malaria in mice. 855 Feb 4

We investigated whether gamma interferon (IFN-gamma; a Th1 cytokine), tumor necrosis factor alpha (TNF-alpha), and interleukin-4 (IL-4; a Th2 cytokine) modulate nitric oxide (NO) production in vivo during blood stage infection with Plasmodium chabaudi AS. Treatment of resistant C57BL/6 mice, which resolve infection with P. chabaudi AS and produce increased levels of IFN-gamma, TNF-alpha, and NO early during infection, with anti-IFN- gamma plus anti-TNF-alpha monoclonal antibodies (MAbs) resulted in a reduction of both splenic inducible NO synthase mRNA and serum NO3- levels by 50 and 100%, respectively. Treatment with the anti-TNF-alpha MAb alone reduced only serum NO3- levels by 35%, and treatment with the anti-IFN-gamma MAb alone had no effect on NO production by these mice during infection. Susceptible A/J mice, which succumb to infection with P. chabaudi AS and produce increased levels of IL-4 but low levels of IFN-gamma, TNF-alpha, and NO early during infection, were treated with an anti-IL-4 MAb. The latter treatment had no effect on NO production by this mouse strain during infection. In addition, our results also demonstrate that treatment of resistant C57BL/6 mice with anti-IFN-gamma plus anti-TNF-alpha MAbs affects, in addition to NO production, other traits of resistance to P. chabaudi AS malaria such as the peak level of parasitemia and the development of splenomegaly. Furthermore, the change in spleen weight was shown to be an IFN-gamma-independent effect of TNF-alpha. Treatment of susceptible A/J mice during infection with an anti IL-4 MAb had no effect on these markers of resistance. Thus, these results demonstrate that TNF-alpha and IFN-gamma are critical in the regulation of NO production and other traits of resistance during P. chabaudi AS malaria in C57BL/6 mice. These data also indicate that treatment with an anti-IL-4 antibody alone is not able to induce NO production or confer resistance to A/J mice against P. chabaudi AS malaria.
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PMID:In vivo regulation of nitric oxide production by tumor necrosis factor alpha and gamma interferon, but not by interleukin-4, during blood stage malaria in mice. 855 72

Mice treated with anti-IFN-gamma monoclonal antibodies were unable to recover from infection with an attenuated variant of P. berghei (Pb XAT) which causes non-lethal malaria in normal mice. On the other hand, treatment with anti-IL-4 monoclonal antibodies had no effect on the course of infection. IFN-gamma was produced by spleen cells in vitro during the early phase of the infection. Treatment with anti-IFN-gamma suppressed development of an anti-plasmodial IgG2a immunoglobulin isotype in the serum of infected mice whereas anti-IL-4 interfered with the IgG1 response. An IgG2a fraction of immune serum collected from mice that had recovered from Pb XAT transferred immunity to naive mice but the IgG1 fraction did not. When glutaraldehyde fixed parasitized erythrocytes were incubated with immune serum in suspension, specific IgG2a antibodies were detected by fluorescein staining on the membranes of cells infected with mature stages of parasites. These results indicate that IFN-gamma is a key to inducing B cells to produce the protective antiplasmodial IgG2a immunoglobulin isotype. Antibody-dependent cell-mediated parasite killing seems to be involved in the mechanism of recovery from infection with Pb XAT.
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PMID:Interferon-gamma and the induction of protective IgG2a antibodies in non-lethal Plasmodium berghei infections of mice. 858 87


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