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PMID: 10456884 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

A defect in interleukin-10 leads to enhanced malarial disease in Plasmodium chabaudi chabaudi infection in mice.

Infection and immunity ·Vol. 67 ·No. 9 ·1999-09-00 ·Pages 4435-42

Li C, Corraliza I, Langhorne J

Abstract

Infection of interleukin-10 (IL-10)-nonexpressing (IL-10(-/-)) mice with Plasmodium chabaudi chabaudi (AS) leads to exacerbated pathology in female mice and death in a proportion of them. Hypoglycemia, hypothermia, and loss in body weight were significantly greater in female IL-10(-/-) mice than in male knockout mice and all wild-type (WT) mice during the acute phase of infection. At this time, both female and male IL-10(-/-) mice produced more gamma interferon (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), and IL-12p40 mRNA than their respective WT counterparts. Inactivation of IFN-gamma in IL-10(-/-) mice by the injection of anti-IFN-gamma antibodies or by the generation of IL-10(-/-) IFN-gamma receptor(-/-) double-knockout mice resulted in reduced mortality but did not affect body weight, temperature, or blood glucose levels. The data suggest that IFN-gamma-independent pathways may be responsible for these pathological features of P. chabaudi malaria and may be due to direct stimulation of TNF-alpha by the parasite. Since male and female knockout mice both produce more inflammatory cytokines than their WT counterparts, it is likely that the mortality seen in females is due to the nature or magnitude of the response to these cytokines rather than the amount of IFN-gamma or TNF-alpha produced.

MeSH Terms
Animals Blood Glucose/analysis Body Temperature Body Weight Disease Models, Animal Erythrocytes Female Interferon-gamma/biosynthesis,blood,genetics Interleukin-10/genetics,immunology Interleukin-12/genetics Interleukin-4/genetics Malaria/immunology,parasitology,physiopathology Male Mice Mice, Inbred C57BL Mice, Knockout Nitric Oxide/biosynthesis Nitric Oxide Synthase/genetics Nitric Oxide Synthase Type II Plasmodium chabaudi/growth & development,immunology RNA, Messenger Receptors, Interferon/genetics,immunology Spleen/cytology Tumor Necrosis Factor-alpha/biosynthesis,genetics
Chemicals
Blood Glucose RNA, Messenger Receptors, Interferon Tumor Necrosis Factor-alpha interferon gamma receptor Interleukin-10 Interleukin-12 Interleukin-4 Nitric Oxide Interferon-gamma Nitric Oxide Synthase Nitric Oxide Synthase Type II Nos2 protein, mouse
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Li C
Imperial College of Science, Technology and Medicine, London SW7 2AZ, United Kingdom.
Corraliza I
Langhorne J
References (52)
52 references, click to expand
  1. Interactions between the gonadal steroids and the immune system.
    Science. 1985 Jan 18;227(4684):257-61 PMID: 3871252
  2. Plasmodium chabaudi chabaudi (AS): inflammatory cytokines and pathology in an erythrocytic-stage infection in mice.
    Exp Parasitol. 1998 Nov;90(3):220-9 PMID: 9806866
  3. Endogenous interleukin-10 modulates proinflammatory response in Plasmodium falciparum malaria.
    J Infect Dis. 1998 Aug;178(2):520-5 PMID: 9697735
  4. Anaemia and resistance to malaria in transgenic mice expressing human tumour necrosis factor.
    Immunology. 1994 Jul;82(3):397-403 PMID: 7959874
  5. Signal transduction in host cells by a glycosylphosphatidylinositol toxin of malaria parasites.
    J Exp Med. 1993 Jan 1;177(1):145-53 PMID: 8418196
  6. Malaria: toxins, cytokines and disease.
    Parasite Immunol. 1995 May;17(5):223-31 PMID: 7675508
  7. The effect of a monoclonal antibody to tumor necrosis factor on survival from childhood cerebral malaria.
    J Infect Dis. 1996 Nov;174(5):1091-7 PMID: 8896514
  8. Interleukin-10-deficient mice develop chronic enterocolitis.
    Cell. 1993 Oct 22;75(2):263-74 PMID: 8402911
  9. TNF concentration in fatal cerebral, non-fatal cerebral, and uncomplicated Plasmodium falciparum malaria.
    Lancet. 1990 Nov 17;336(8725):1201-4 PMID: 1978068
  10. Specificity of hypoglycaemia for cerebral malaria in children.
    Lancet. 1990 Aug 25;336(8713):454-7 PMID: 1974988
  11. Steroid sex hormones regulate the release of tumor necrosis factor by macrophages.
    Cell Immunol. 1995 Jan;160(1):43-9 PMID: 7842485
  12. Proposed link between cytokines, nitric oxide and human cerebral malaria.
    Parasitol Today. 1991 Aug;7(8):205-7 PMID: 15463497
  13. Variation in the TNF-alpha promoter region associated with susceptibility to cerebral malaria.
    Nature. 1994 Oct 6;371(6497):508-10 PMID: 7935762
  14. L3T4+ T lymphocytes play a major role in the pathogenesis of murine cerebral malaria.
    J Immunol. 1986 Oct 1;137(7):2348-54 PMID: 3093572
  15. Tumour necrosis factor may contribute to the anaemia of malaria by causing dyserythropoiesis and erythrophagocytosis.
    Br J Haematol. 1988 Sep;70(1):99-103 PMID: 3179231
  16. Monoclonal antibody against interferon gamma can prevent experimental cerebral malaria and its associated overproduction of tumor necrosis factor.
    Proc Natl Acad Sci U S A. 1989 Jul;86(14):5572-4 PMID: 2501793
  17. A polymorphic dinucleotide repeat in the human IL-10 promoter.
    Immunogenetics. 1995;42(5):444-5 PMID: 7590988
  18. IL-10 is required to prevent immune hyperactivity during infection with Trypanosoma cruzi.
    J Immunol. 1997 Apr 1;158(7):3311-6 PMID: 9120288
  19. Interleukin-10 modulates susceptibility in experimental cerebral malaria.
    Immunology. 1997 Aug;91(4):536-40 PMID: 9378491
  20. Helicobacter hepaticus triggers colitis in specific-pathogen-free interleukin-10 (IL-10)-deficient mice through an IL-12- and gamma interferon-dependent mechanism.
    Infect Immun. 1998 Nov;66(11):5157-66 PMID: 9784517
  21. Role of gamma interferon during infection with Plasmodium chabaudi chabaudi.
    Infect Immun. 1990 Nov;58(11):3671-8 PMID: 1977706
  22. Cerebral malaria in inbred mice. I. A new model and its pathology.
    Trans R Soc Trop Med Hyg. 1982;76(3):410-5 PMID: 7051459
  23. Estrogen regulates the IFN-gamma promoter.
    J Immunol. 1991 Jun 15;146(12):4362-7 PMID: 1904081
  24. Sex hormones, immune responses, and autoimmune diseases. Mechanisms of sex hormone action.
    Am J Pathol. 1985 Dec;121(3):531-51 PMID: 3907369
  25. Standardization of mRNA titration using a polymerase chain reaction method involving co-amplification with a multispecific internal control.
    J Biol Chem. 1992 Oct 25;267(30):21830-8 PMID: 1400493
  26. Dietary testosterone suppresses protective responsiveness to Plasmodium chabaudi malaria.
    Life Sci. 1997;60(11):839-48 PMID: 9076323
  27. Genetic influence on cytokine production and fatal meningococcal disease.
    Lancet. 1997 Jan 18;349(9046):170-3 PMID: 9111542
  28. Tumour necrosis factor and interleukin-6 production induced by components associated with merozoite proteins of Plasmodium falciparum.
    Parasite Immunol. 1993 Apr;15(4):229-37 PMID: 8506119
  29. Tumor necrosis factor and disease severity in children with falciparum malaria.
    N Engl J Med. 1989 Jun 15;320(24):1586-91 PMID: 2657427
  30. Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids.
    Anal Biochem. 1982 Oct;126(1):131-8 PMID: 7181105
  31. Role of interleukin-10 in regulation of T-cell-dependent and T-cell-independent mechanisms of resistance to Toxoplasma gondii.
    Infect Immun. 1997 May;65(5):1675-82 PMID: 9125546
  32. Hormonal regulation of immune responses.
    Ann Med. 1994 Aug;26(4):255-8 PMID: 7946244
  33. Malaria mimicry with tumor necrosis factor. Contrasts between species of murine malaria and Plasmodium falciparum.
    Am J Pathol. 1992 Feb;140(2):325-36 PMID: 1739126
  34. New derivative of pMUS for quantitation of mouse IL-12 (p35, p40), IL-10 and IFN-gamma-R mRNAs.
    Eur Cytokine Netw. 1994 May-Jun;5(3):337-8 PMID: 7948769
  35. Resistance to Plasmodium chabaudi in B10 mice: influence of the H-2 complex and testosterone.
    Infect Immun. 1988 Sep;56(9):2400-6 PMID: 3410544
  36. Immune response in mice that lack the interferon-gamma receptor.
    Science. 1993 Mar 19;259(5102):1742-5 PMID: 8456301
  37. Severe malarial anemia and cerebral malaria are associated with different tumor necrosis factor promoter alleles.
    J Infect Dis. 1999 Jan;179(1):287-90 PMID: 9841857
  38. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.
    Anal Biochem. 1987 Apr;162(1):156-9 PMID: 2440339
  39. Low plasma concentrations of interleukin 10 in severe malarial anaemia compared with cerebral and uncomplicated malaria.
    Lancet. 1998 Jun 13;351(9118):1768-72 PMID: 9635949
  40. Production of interferon-gamma during infection of mice with Plasmodium chabaudi chabaudi.
    Immunobiology. 1989 Oct;179(4-5):353-65 PMID: 2515153
  41. Cytokine profiles for human V gamma 9+ T cells stimulated by Plasmodium falciparum.
    Parasite Immunol. 1995 Aug;17(8):413-23 PMID: 7501422
  42. The biological basis of malarial disease.
    Int J Parasitol. 1997 Oct;27(10):1237-49 PMID: 9394194
  43. Interleukin-10.
    Annu Rev Immunol. 1993;11:165-90 PMID: 8386517
  44. A low interleukin-10 tumor necrosis factor-alpha ratio is associated with malaria anemia in children residing in a holoendemic malaria region in western Kenya.
    J Infect Dis. 1999 Jan;179(1):279-82 PMID: 9841855
  45. Anti-TNF therapy inhibits fever in cerebral malaria.
    Q J Med. 1993 Feb;86(2):91-8 PMID: 8329024
  46. Frequencies of CD4+ T cells reactive with Plasmodium chabaudi chabaudi: distinct response kinetics for cells with Th1 and Th2 characteristics during infection.
    Int Immunol. 1989;1(4):416-24 PMID: 2535135
  47. In the absence of endogenous IL-10, mice acutely infected with Toxoplasma gondii succumb to a lethal immune response dependent on CD4+ T cells and accompanied by overproduction of IL-12, IFN-gamma and TNF-alpha.
    J Immunol. 1996 Jul 15;157(2):798-805 PMID: 8752931
  48. Roles of CD4- and CD8-bearing T lymphocytes in the immune response to the erythrocytic stages of Plasmodium chabaudi.
    Infect Immun. 1988 Dec;56(12):3081-8 PMID: 2903123
  49. A Th1-associated increase in tumor necrosis factor alpha expression in the spleen correlates with resistance to blood-stage malaria in mice.
    Infect Immun. 1996 Feb;64(2):535-41 PMID: 8550204
  50. Plasmodium chabaudi chabaudi: differential susceptibility of gene-targeted mice deficient in IL-10 to an erythrocytic-stage infection.
    Exp Parasitol. 1996 Nov;84(2):253-63 PMID: 8932775
  51. Tumor necrosis factor (cachectin) as an essential mediator in murine cerebral malaria.
    Science. 1987 Sep 4;237(4819):1210-2 PMID: 3306918
  52. The solubility of amino acids, diglycine, and triglycine in aqueous guanidine hydrochloride solutions.
    J Biol Chem. 1970 Apr 10;245(7):1648-52 PMID: 5438355
Article Info
Journal
Infection and immunity
Abbr.
Infect Immun
ISSN
0019-9567
DOI
10.1128/IAI.67.9.4435-4442.1999
Published
1999-09-00
Pages
4435-42
Language
English
Region
United States
NLM ID
0246127
PMCID
PMC96762
Subset
IM
Grants
Wellcome Trust · United Kingdom
External Links
PubMed source DOI: 10.1128/IAI.67.9.4435-4442.1999 PMC Full Text View journal details
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