DOES MALARIAL TOLERANCE, THROUGH NITRIC-OXIDE, EXPLAIN THE LOW INCIDENCE OF AUTOIMMUNE-DISEASE IN TROPICAL AFRICA

Autoimmune disease is generally rare in tropical rural populations. Pl asma concentrations of nitrite plus nitrate (reactive nitrogen interme diates), reflecting high nitric-oxide production somewhere in the body , can be high in patients who have cerebral malaria, but even higher i n symptom-free parasitised individuals, who are termed malaria-toleran t. We propose that the nitric oxide causing high serum levels of react ive nitrogen intermediates in malaria-tolerant individuals is generate d in macrophages during the establishment and maintenance of malarial tolerance, and makes autoimmune disease rare in many tropical rural po pulations by minimising proliferation of autoreactive T cells. Convers ely, innately low levels of nitric-oxide generation in these populatio ns, selected by malarial disease in tropical areas, could rationalise their high frequency of autoimmune disease and hypertension when livin g in western societies.