Seasonal changes in phytohemagglutinin-induced cytokine synthesis by peripheral blood lymphocytes of patients with seasonal allergic rhinitis due to Japanese cedar pollens. Acta Otolaryngol (Stockh) 1998; Suppl 538: 156-168.We investigated the seasonal changes in non-specific stimulation-induced cytokine production by peripheral blood mononuclear cells (PBMCs) in patients with seasonal allergic rhinitis due to Japanese cedar pollen. This study included 16 non-allergic healthy adult volunteers and 115 patients with detectable levels of Japanese cedar pollen-specific IgE in their serum. The 115 patients were divided into five groups, an asymptomatic group (specific IgE was positive but there were no nasal symptoms), a medication group (typical symptoms of Japanese cedar pollinosis and treated with antihistamine tablets), a good-IT group (responded well to immunotherapy), a poor-IT group (responded poorly to immunotherapy) and a cure group (no symptoms after discontinuation of immunotherapy). PBMCs (1.0 ×10 6 cells/ml) were collected before and during the cedar pollen season in 1998, and were cultured for 24 h in the presence of 10 vg/ml phytohemagglutinin. The concentrations of IL-4, IL-5 and IFN-g in the culture supernatants were measured by an enzyme-linked immunosorbent assay. None of the levels of IL-4, IL-5 and IFN-g synthesized by PBMCs in the asymptomatic group, medication group, good-IT group, poor-IT group or cure group were significantly different from those in the non-atopic group. In the medication group, the synthesis of TH2-type cytokines (both IL-4 and IL-5), but not of TH1-type cytokine (IFN-g) was significantly increased during the pollen season compared with before the pollen season, whereas in the non-atopic group, the synthesis of IL-4, IL-5 and IFN-g did not differ significantly before and during the pollen season. The synthesis of both IL-4 and IL-5 was significantly increased during the pollen season in the poor-IT group, whereas the synthesis of IL-4 and IL-5 was not increased during the pollen season in the good-IT or cure groups. In conclusion, our study demonstrates that T-cell reactivity to non-specific stimulation outside of the pollen season did not differ between the patients with seasonal allergic rhinitis and non-atopic individuals, that T-cells in patients with seasonal allergic rhinitis are affected or primed by the natural pollen exposure to synthesize TH2-type cytokines even in response to non-specific stimulation, and that successful immunotherapy could decrease the natural pollen exposureprimed hyperreactivity of TH2 cells to non-specific stimulants. Key words: immunotherapy, interferon-gamma, interleukin-4, interleukin-5, peripheral blood mononuclear cells.