AMELIORATION OF MURINE CEREBRAL MALARIA BY DIETARY RESTRICTION

CBA/T6 strain mice infected with Plasmodium berghei ANKA develop cerebral symptoms and die, with mononuclear cell attachment to the cerebral microvascular endothelium, petechial haemorrhages and breakdown of the blood-brain barrier, some 6-7 days post-inoculation. The effects of dietary restriction on this process were examined. Mice were fed ab libitum (Group 1) or their food was restricted to produce body weight loss of 1.0-2.0 % (Group 2), 2.5-3.5 % (Group 3), 4.0-6.5 % (Group 4) or 7.0-9.5 % (Group 5) relative to Group 1. Dietary restriction reduced deaths caused by cerebral malaria from 100 % in Group 1 to 47 % (Group 2), 43 % (Group 3), 10 % (Group 4) and 53 % (Group 5). Restriction of food intake had no effect on (1) the progression of parasitaemia in infected mice (2) changes in haematocrit, spleen weight, total lymph node cell number or (3) peritoneal exudate cell number in either malaria-infected or uninfected mice. P. berghei ANKA infection did not significantly affect the proportion of lymph node leucocytes that were Thy-1+ T cells or CD8+ T cells, but did lead to significant increases in the CD4+ and B cell populations. Dietary restriction alone increased the lymph node CD4+ cell population but did not affect the increase in B cells in malaria-infected mice. P. berghei ANKA infection and dietary restriction together did not lead to increased CD4+ cell numbers in lymph node leucocytes. The in vitro proliferative response of isolated lymph node cells to concanavalin A or phorbol myristate acetate plus ionomycin was measured and found to be identical in all treatment groups. Plasma levels of tumour necrosis factor (TNF) increased from undetectable in uninfected mice or P. berghei ANKA-infected mice on days 1-6 post-inoculation to 21 +/- 2 ng/ml on day 7 when cerebral symptoms were at their height and death was imminent. This increase in plasma TNF was substantially inhibited in those mice subjected to regimes of dietary restriction. There was a good correlation (r2 = 0.73) between plasma TNF level and percentage mortality in the 5 treatment groups. The results indicate that dietary status is an important factor in the outcome of murine cerebral malaria and perhaps, by extrapolation, in the human disease.