John R. David

Research

Our groups two main research interests are the immunobiology of cytokines and the control of parasitic infections with a focus on leishmaniasis, We produced recombinant migration inhibitory factor (rMIF), the first lymphokine discovered in the 1960s, and are determining the biological role of the 12kD recombinant cytokine. RMIF has marked effects on the physiology of macrophages, a cell important in the afferent limb of the immune response and in mechanisms of inflammation. Studies by others have shown the presence of MIF-MRNA in numerous cell types suggesting it has other functions as well. They have shown that MIF is important in the pathogenesis of endotoxic shock, inhibits the antiinflammatory effects of corticosteroids, plays a role in the development of the eye, and enhances the secretion of insulin.

Our current studies are focused on understanding the functions of MIF in a genetic-deficient strain of mice that we have recently developed that lacks the MIF gene.

Studies on parasitic diseases now focus on leishmaniasis. Early studies emphasized the bringing of new diagnostic techniques from the laboratory to the field. Recent studies In Brazil have focused on using these techniques to understand the mechanisms of transmission, including defining the importance of dogs as reservoir hosts for leishmaniasis and developing control strategies and trials for immunotherapy and radiowave-induced heat therapy for cutaneous leishmaniasis. In Boston, the work has focused on understanding the mechanisms of immunity using mice that are genetically deficient in cytokines, their receptors, or other relevant molecules, and on maxadilan, a recombinant peptide from the saliva of sand flies, the insect that transmits leishmaniasis. Maxadilan is a potent vasodilator and immunosuppressive molecule which appears to be necessary for the transmission of leishmaniasis. It also can completely prevent the lethal effects of LPS induced endotoxin shock in mice.