MYCOBACTERIAL HEAT-SHOCK PROTEIN-65 INDUCES PROINFLAMMATORY CYTOKINESBUT DOES NOT ACTIVATE HUMAN MONONUCLEAR PHAGOCYTES

The 65 kDa heat-shock protein (Hsp65), a well-conserved and immunodomi nant antigen which elicits a cellular and humoral immune response, may play a role in host defence against invading microorganisms and autoi mmune disorders. The aim of the present study was to assess the effect s of Hsp65 on the functional activities of human mononuclear phagocyte s in the absence of lymphocytes. Incubation with Hsp65 resulted in an enhanced release of TNF-alpha and IL-1 beta by human monocytes and mon ocyte-derived macrophages (MDM). The amount of cytokines released by t hese cells in response to Hsp65 was similar to that released in respon se to IFN-gamma together with LPS. Incubation with ovalbumin did not s timulate the release of these cytokines. In vitro stimulation of monoc ytes with Hsp65 enhanced the membrane expression of complement recepto r III but did not influence either the expression of Fc gamma-receptor I and HLA class-II antigens or the release of reactive oxygen interme diates. Therefore, Hsp65-stimulated monocytes cannot be considered to be activated according to classical criteria. The release of the proin flammatory cytokines TNF-alpha and IL-1 beta by human mononuclear phag ocytes in response to Hsp65 indicates that this protein can contribute to both host defence and tissue damage in inflammatory lesions charac terized by an abundant expression of Hsp65.