CORTICOSTEROIDS RESTORE THE BALANCE BETWEEN LOCALLY PRODUCED TH1 AND TH2 CYTOKINES AND IMMUNOGLOBULIN ISOTYPES TO NORMAL IN SARCOID LUNG

In this study, we have investigated the balance between Th1- and Th2-l ike activity in the lungs in sarcoidosis and have determined the effec t of corticosteroid treatment on this. Twenty-one patients with acute untreated sarcoidosis were investigated by bronchoalveolar lavage (BAL ) and compared with 11 normal volunteers. Sixteen of the sarcoid patie nts required corticosteroid therapy and seven of these were reinvestig ated after 2-3 months' treatment. In order to assess Th1- and Th2-like activity in the lungs, IgG subclasses and IgE were measured in BAL fl uid and serum, and IL-2, IL-4 and interferon-gamma (IFN-gamma) in BAL. In patients with untreated sarcoidosis, albumin-corrected BAL/serum r atios for IgG4 and IgE were significantly reduced (IgG4, 1.04 +/- 0.18 (mean +/- s.e.m.); IgE 9.58 +/- 3.11) compared with those in normal c ontrols (IgG4 5.3 +/- 0.72, P < 0.001; IgE 67.7 +/- 28.9, P +/- 0.01). Estimates of actual levels of immunoglobulins produced in the lungs w ere also made and showed extremely high levels of total IgG in sarcoid patients (39.56 +/- 8.2 mg/l) compared with controls (1.17 +/- 0.5 mg /l, P < 0.001). Although there was no difference between the groups in amount of IgG4 locally produced, the proportion of total IgG which wa s IgG4 was greatly reduced in those with sarcoidosis (1.6 +/- 0.4% com pared with 38.5 +/- 3.2%; P < 0.001). Lavage levels of IL-4 were also reduced in sarcoid patients (IL-4 2.103 +/- 0.21 pg/ml) compared with those in normals (IL-4 6.8 +/- 1.05; P < 0.001). Levels of IL-2 were l ower (7.63 +/- 0.51 pg/ml compared with 9.4 +/- 0.95 pg/ml), but this difference was not significant. IFN-gamma, however, could not be detec ted above 0.4 pg/ml in any of the (chi(2) = 7.74; P < 0.001). These no rmal lavage fluid, but was detectable in 12/21 patients with sarcoidos is (chi(2) changes reverted towards normal on treatment with oral cort icosteroids. The mean albumin-corrected BAL/serum ratio for IgG4 befor e treatment was 0.88 +/- 0.33 compared with 5.5 +/- 2.1 (P < 0.05) on treatment, and for IgE before treatment 9.52 +/- 2.15 compared with 50 .8 +/- 17.9 (P < 0.05) on treatment. Total IgG produced in the lung fe ll from 26.16 +/- 7.9 to 6.12 +/- 2.4 mg/l (P < 0.001) on treatment, a nd the proportion of IgG4 locally produced rose from 2.3 +/- 0.8% to 2 3.9 +/- 6.1% (P < 0.01). The mean level of IL-4 in lavage before treat ment was 2.53 +/- 0.34 pg/ml compared with 4.7 +/- 0.34 (P < 0.001) on treatment. Levels of IL-2 also rose significantly on treatment from 8 .74 +/- 0.95 pg/ml before to 14.44 +/- 1.38 pg/ml (P < 0.001) on treat ment. Levels of IFN-gamma fell from 1.65 +/- 0.43 pg/ml before treatme nt to undetectable levels in all patients (P < 0.001) on treatment. Th ese results demonstrate an imbalance between Th1- and Th2-like activit y in the lungs in sarcoidosis, with suppression of Th2 and increase in Th1. Corticosteroid therapy restores the normal balance between Th1 a nd Th2 cytokines and immunoglobulins in the lungs, suggesting an effec t on local immune regulation.