Inhibition of delayed hypersensitivity reactions by a new agent, cis-1-methyl-4-isohexylcyclohexane carboxylic acid (IG-10)—II. The mechanism regarding the action on lymphokines

A newly synthesized anti-allergic agent, cis-1-methyl-4-isohexylcyclohexane carboxylic acid (IG-10), has the capacity to inhibit the effector phase of delayed hypersensitivity reactions. In the present paper, the effect of IG-10 was studied on the generation of superoxide anion (O 2 -) from macrophages, on macrophage chemotaxis, and on the activity of lymphokines such as skin reactive factor (SRF), macrophage migration inhibitory factor (MIF) and monocyte/macrophage chemotactic factor (MCF) in guinea pigs. Oral administration of IG-10 (50–200 mg/kg) inhibited SRF-induced skin erythema in a dose-dependent manner. In vitro, this agent (10 -7 - 10 -5 g/ml) did not inhibit the generation of O 2 - from macrophages. The agent (10 -7 - 10 -6 g/ml) significantly inhibited the activity of MIF and this inhibition was not due to the facilitation of normal migration. For macrophage chemotaxis, IG-10 (10 -8 - 10 -6 g/ml) significantly inhibited MCF-induced chemotaxis. The agent also depressed the macrophage chemotaxis induced by N-formyl-methionyl-leucyl-phenylalanine but not the chemotaxis induced by E. coli culture filtrate. The inhibitory action of IG-10 on MCF activity was not influenced by antiglucocorticoid agents such as 17α-methyltestosterone and androstenedione which reverse significantly the inhibitory action of glucocorticoids. The inhibitory action of IG-10 was relatively dependent on exogenous Ca 2+ and Mg 2+, and was antagonized by dbc-GMP.