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Effects of glucocorticoids on human neutrophil responses to leukocyte migration inhibition factor (LIF) and neutrophil chemokinesis were examined using an agarose gel technique. The roles of endogenous monohydroxyeicosatetraenoic acids (HETE) and prostaglandins (PG) in basal neutrophil chemokinesis were also examined. Methylprednisolone sodium succinate (MPSS) in concentrations up to 200 micrograms/ml failed to inhibit the neutrophil response to LIF. MPSS enhanced neutrophil chemokinesis in a dose-related manner at concentrations from 2 micrograms/ml to 200 micrograms/ml (P less than 0.01). Since inhibition of membrane phospholipase activity by MPSS is known to decrease production of HETE and PG, the present data suggest that HETE and PG do not mediate basal neutrophil chemokinesis. This was confirmed by selectively inhibiting HETE production with the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA) or PG production with the cyclooxygenase inhibitor indomethacin. Neutrophil chemokinesis was unaffected by 10(-5) M NDGA (P less than 0.05) or 10(-5) indomethacin (P less than 0.05).

The effects of the lymphokine, leukocyte inhibitory factor (LIF), on human neutrophil function were studied. This soluble mediator, which is defined by its specific inhibition of neutrophil locomotion, does not interfere with chemotactic factor binding and does not affect basal or stimulated superoxide generation by neutrophils. In contrast, phagocytosis of opsonized Staphylococcus aureus is markedly inhibited by LIF, and degranulation is stimulated by this lymphokine. The possible mechanisms of LIF action on neutrophils are discussed.