The objective of this study was to investigate the effect of interleukin-8 (IL-8) and RANTES on basophil histamine release induced with monocyte chemoattractant peptide-1 (MCP-1) and crude histamine releasing factor (HRF). IL-8 induced low levels of histamine release (8.5 +/- 0.5%) from basophils obtained from only six of 20 donors at high concentrations (10(-6) M). RANTES induced histamine release (16 +/- 2%) from basophils of four of 15 donors at 10(-7) M concentration. However, both IL-8 and RANTES inhibited MCP-1 and HRF-induced histamine release from basophils dose-dependently at concentrations of 10(-9) to 10(-7) M. Basophils from all donors showed a significant inhibitory response (greater than 15%). The maximal inhibition of MCP-1 and HRF by IL-8 was 28 +/- 4% and 48 +/- 8%, respectively. The maximal inhibition of MCP-1 and HRF by RANTES was 26 +/- 4% and 43 +/- 6%, respectively. Peripheral blood mononuclear cell-derived HRF was purified into three distinct peaks by reverse-phase high performance liquid chromatography. Peak I contained MCP-1 as judged by binding to an immunoaffinity column that was prepared with anti-MCP-1 antibody. IL-8 inhibited histamine release induced with all three peaks of HRF. The inhibition of histamine release by IL-8 was significantly higher in normal subjects than in allergic patients (59 +/- 9% versus 31 +/- 7%, P less than 0.05). Both IL-8 and RANTES inhibited cytokine-induced histamine release only and did not affect histamine release by anti-IgE, FMLP, and C5a.(ABSTRACT TRUNCATED AT 250 WORDS)