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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.

Original publication




Journal article


Lancet (London, England)

Publication Date





1492 - 1494


Division of Biochemistry and Molecular Biology, School of Life Sciences, Australian National University, Canberra, Australia.


T-Lymphocytes, Macrophages, Humans, Malaria, Cerebral, Malaria, Autoimmune Diseases, Nitrates, Nitrites, Nitric Oxide, Immunosuppression, Tropical Climate, Immune Tolerance, Africa