Interleukin-1, platelet derived growth factor, free radicals and monocyte aryl hydrocarbon hydroxylase activity in liver disease. Role of cell communication

Monocytes were isolated from blood of human origin and cultured in supplemented Leibovitz (l-15) medium for 24 hr. The medium was then decanted and filtered, and all subsequent tests were done on monocyte conditioned medium (MCM). The monocytes of patients with liver disease spontaneously secrete temperature-sensitive arylhydrocarbon hydroxylase (AHH) inhibitory factors detectable in the MCM. Anti-interleukin-1 antibody (IL-lAb) reduced the AHH inhibitory activity of the MCM, suggesting that part of the AHH inhibitory activity was due to interleukin-1 (IL-1). Platelet derived growth factor did not affect AHH activity. Interleukin-1β was detectable in MCM but did not differ significantly between patients and normal volunteers. A time course experiment indicated that interleukin-1β inhibited hepatocyte AHH activity after only 2 hr of incubation. Catalase partially blocked the AHH inhibitory activity of MCM suggesting that activated oxygen intermediates are partially involved in the AHH inhibitory activity of the MCM. Simultaneous incubation of interleukin-1β and catalase did not prevent or augment the inhibitory action of IL-1 on AHH activity. IL-1 stimulates collagen synthesis and elevates serum procollagen type 3 peptide (P-III-P). Results indicated that serum P-III-P was elevated in blood sources producing temperature-sensitive AHH inhibitory factor.