M-CSF PRODUCTION BY HIV-1-INFECTED MONOCYTES AND ITS INTRATHECAL SYNTHESIS IMPLICATIONS FOR NEUROLOGICAL HIV-1-RELATED DISEASE

Macrophage-colony stimulating factor (M-CSF) is detectable in the cere brospinal fluid (SF) of HIV-1-infected patients, and may be produced i ntrathecally by both reactive astrocytes and cells of the monocyte/mac rophage (MO) lineage, microglial cells included. Since MO constitute t he target cells for HIV-1 in the central nervous system (CNS), the cul ture conditions that induce M-CSF production by HIV-1-infected MO were studied. MO cultures infected with supernatants (SN) of HIV-2-infecte d peripheral blood lymphocyte (PBL) cultures produced only trace or un detectable amounts of M-CSF. Co-cultures of MO with normal PBL release d high amounts of M-CSF, suggesting that viable cell-to-cell interacti ons are required to induce cytokine production by MO and/or PBL. M-CSF production was markedly increased in the MO co-cultured with HIV-1-in fected PBL, thus implying that HIV-1 induces increased cytokine synthe sis/release by MO and/or PBL only when cell membrane-associated messag es are operating. Intracerebrally synthesized M-CSF by HIV-1-infected MO may play a role in promoting viral replication/spread within the CN S, and inducing brain damage by stimulating microglia proliferation, a nd neurotoxic factor release by these cells.