ADHESION OF PLASMODIUM-FALCIPARUM-INFECTED ERYTHROCYTES TO HUMAN-CELLS AND SECRETION OF CYTOKINES (IL-1-BETA, IL-1RA, IL-6, IL-8, IL-10, TGF-BETA, TNF-ALPHA, G-CSF, GM-CSF)

The scientific interest in the physical interaction of Plasmodium falc iparum-infected erythrocytes with host cells stems from the suggestion that excessive binding in the microvasculature leads to severe malari a. The authors studied, therefore, two parasites for their ability to adhere to normal human cells and to induce cytokine production, one pa rasite lacking a binding capacity (DD2) and one which adhered to CD36( +) transfected CHO cells (MCAMP). The MCAMP parasites readily bound to platelets and erythrocytes and to monocytes, polymorphonuclear granul ocytes and EBV-transformed B cells as seen by light and electron micro scopy. Platelets were frequently attached in large numbers to the infe cted erythrocyte surface and groups of infected erythrocytes were some times held together by several platelets. Nine out of 17 cytokines tes ted were found to be secreted into the culture supernatants after 35 h of co-cultures containing monocytes or unfractionated peripheral bloo d mononuclear cells (PBMC) and parasites (IL-1RA, IL-6, IL-8, IL-10, T GF beta, TNF alpha, G-CSF, IL-1-beta, and GM-CSF). Three additional cy tokines were also present in low levels (<200 pg/ml, IL-2, IL-4, IFN g amma) in the culture supernatants after incubation of the cells for 4 days. TNF alpha, IL-RA, and IL-8 were secreted from polymorphonuclear granulocytes, LGLs and T cells. Platelets and, to a lesser degree, mon ocytes and T cells secreted large amounts of TGF beta (10-30 ng/ml). C ytokines may participate in the pathogenesis but also the suppression of immune responses seen during acute malarial infections.