IN-VITRO MODULATION OF KERATINOCYTE-DERIVED INTERLEUKIN-1-ALPHA (IL-1-ALPHA) AND PERIPHERAL-BLOOD MONONUCLEAR CELL-DERIVED IL-1-BETA RELEASE IN RESPONSE TO CUTANEOUS COMMENSAL MICROORGANISMS

The ability of a range of skin commensal microorganisms to modulate in terleukin-l (IL-1) release by cultured human keratinocytes and periphe ral blood mononuclear cells (PBMCs) was investigated by a combination of enzyme-linked immunosorbent assays and bioassays, Three fractions ( formaldehyde-treated whole cells, culture supernatants, and cellular f ractions) were prepared from Propionibacterium acnes, Propionibacteriu m granulosum, Staphylococcus epidermidis, Staphylococcus capitis, Stap hylococcus hominis, and Malassezia furfur serovar B. The levels of imm unochemical IL-1 alpha released by cultured keratinocytes during coinc ubations with these microbial fractions ranged from 0 to 136 pg/ml and were maximal after 72 h. No microbial fraction consistently upregulat ed immunochemical IL-alpha release by freshly isolated keratinocytes f rom two donors and a transformed cell line, all of which produced the cytokine constitutively to various extents, Bioassays revealed that mo st of the IL-1 released was biologically inactive, In contrast, whole cells of formaldehyde-treated P. granulosum and S. epidermidis signifi cantly stimulated release of IL-1 beta by PBMCs from three donors comp ared with the negative control (culture medium), Release was maximal a t 24 h, Coincubation with intact cells of the yeast M. furfur signific antly decreased levels of IL-beta below the values for the negative co ntrol by PBMCs from all three donors. There was good correlation betwe en bioassay data and immunoassay data for IL-1 beta, and the depressiv e effect of M. furfur cells on cytokine production by all three cultur es of PBMCs was mirrored in the levels of bioactive cytokine. This red uction in IL-1 beta release by PBMCs by M, furfur may provide an expla nation why dermatoses thought to be caused by this yeast are essential ly noninflammatory or only mildly inflammatory.