title: Does malarial tolerance, through nitric oxide, explain the low incidence of autoimmune disease in tropical Africa?
abstract: Autoimmune disease is generally rare in tropical rural populations. Plasma concentrations of nitrite plus nitrate (reactive nitrogen intermediates), reflecting high nitric-oxide production somewhere in the body, can be high in patients who have cerebral malaria, but even higher in symptom-free parasitised individuals, who are termed malaria-tolerant. We propose that the nitric oxide causing high serum levels of reactive nitrogen intermediates in malaria-tolerant individuals is generated in macrophages during the establishment and maintenance of malarial tolerance, and makes autoimmune disease rare in many tropical rural populations by minimising proliferation of autoreactive T cells. Conversely, innately low levels of nitric-oxide generation in these populations, selected by malarial disease in tropical areas, could rationalise their high frequency of autoimmune disease and hypertension when living in western societies.
authors.affiliation: Division of Biochemistry and Molecular Biology, School of Life Sciences, Australian National University, Canberra, Australia.
authors.forename: I A
authors.initials: IA
authors.lastname: Clark
authors.forename: F M
authors.initials: FM
authors.lastname: al-Yaman
authors.forename: W B
authors.initials: WB
authors.lastname: Cowden
authors.forename: K A
authors.initials: KA
authors.lastname: Rockett
mesh_terms: D000349:Africa / Q000453:epidemiology; D001327:Autoimmune Diseases / Q000453:epidemiology* / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D007165:Immunosuppression Therapy; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008288:Malaria / Q000276:immunology* / Q000469:parasitology; D016779:Malaria, Cerebral / Q000378:metabolism / Q000469:parasitology; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000378:metabolism* / Q000502:physiology; D009573:Nitrites / Q000097:blood; D013601:T-Lymphocytes / Q000276:immunology; D014329:Tropical Climate
chemical_list: D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide