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In an effort to determine the impact of halothane anesthesia on certain human cell-mediated immune functions, normal, purified human monocytes and lymphocytes were exposed to halothane in vitro at varying concentrations for up to 8 hours. Subsequently, these human effector cells were analyzed for their ability to function in several cell-mediated immunologic assays. Natural killer cell activity against K-562 was unaffected by halothane in most of the donors tested. Similarly, the ability of purified monocytes to inhibit MBL-2 tumor cell growth was unchanged. Halothane appeared to decrease the proliferative response of lymphocytes to phytohemagglutinin (PHA) in approximately 50% of the normal donors tested. In contrast, the ability of monocytes to lyse antibody-coated red cell targets (ADCC) was unaffected by even maximal exposure to halothane. Of interest was the finding that human monocytes exposed to as low as 2% halothane anesthesia for 4 hours displayed a dramatic down-regulation of hydrogen peroxide (H2O2) release. Since it is known that hydrogen peroxide and other incompletely reduced forms of oxygen secreted by monocytes can play a major role in the antimicrobial, antitumor, and inflammatory functions of these cells, this finding may help explain the enhanced susceptibility of post-operative patients to infections.

Prostaglandins of the E series (PGE), produced by mononuclear phagocytes, have many biological activities and are involved in the regulation of myelopoiesis and of the cytotoxic activities of macrophage (M+) and natural killer (NK) cells. Since one of the possible effects of biological response modifiers (BRMs) on immune regulation might be modulation of PGE production, resident peritoneal murine M+ (mMψ) and elutriated human blood mono-cytes (hM) were incubated with BRMs and the supernatants were then assayed for PGE. Control mMψ produced about 4.9 ng PGE/105 mMψ over a 24 hr period. Lipopolysaccharide (LPS, 1-5 μg/ml), polyinosinic-polycytidylic acid complexed with poly-L-lysine (Poly ICLC, 0.1-10 μg/ml) and murine α,β-interferon, (IFN, 10-1000 μ/ml) all caused a highly significant increase in PGE-secretion. BM41.332, a 2-cyanoaziridine (25-50 μg/ml), was found to be less stimulatory, whereas the pyran copolymer MVE-2 (25-50 μg/ml), and Azimexone (25-50 μg/ml) had marginal effects on PGE-production. Kinetic studies showed that the plateau of PGE-production by mMψ occurred during the first 24 hr of incubation, and mMψ which were washed after a 24 hr incubation period could not be restimulated to produce more PGE. PGE release by hM was increased after stimulation with LPS, Poly ICLC and BM41.332, whereas human IFNs (α and β) induced a slight decrease in PGE production. As in the murine studies, Azimexone and MVE-2 had no detectable effect. The ability of some BRMs to augment PGE-secretion by mMψ and hM may contribute to their negative effects on host responses, such as suppression of NK cell activity.