The antimicrobial peptide, cathelicidin, is considered to be critical to innate immunity in alveolar macrophages. In sarcoidosis, a chronic granulomatous disease of unknown etiology, pro-inflammatory cytokines, such as interferon-gamma (IFN-γ) are overproduced. Previous reports suggest elevation of 1, 25 dihydroxyvitamin D (1, 25 vitD) in sarcoidosis, and implicated IFN-γ as a promoter of 1, 25 vitD, now known to be a potent cathelicidin inducer.
Based on such data, we hypothesized an increase in cathelicidin expression in sarcoidosis bronchoalveolar lavage (BAL) cells compared to healthy controls. BAL cells from patients with biopsy proven sarcoidosis (n = 26), and healthy controls (n = 18) were analyzed for messenger ribonucleic acid (mRNA) expression of cathelicidin, (IFN-γ), and the vitamin D receptor (VDR) by quantitative PCR. Sarcoidosis was classified as severe (requiring systemic therapy), or non-severe (never required systemic therapy). Circulating vitD and 1, 25 vitD levels were also determined.
Compared to healthy controls, cathelicidin mRNA expression was 30% lower in BAL cells of patients with severe sarcoidosis (n = 14, p < 0.002); and 14% lower in patients with non-severe disease (n = 12, p = 0.037). VDR mRNA expression of either group did not differ from controls. Circulating vitD was lower in severe than in non-severe patients (p < 0.05) and values for both groups were below the recommended normal level (30ng/ml). Circulating 1, 25 vitD levels, however were within normal range (22–67pg/ml). IFN-γ, as anticipated was higher than controls (p = 0.009), and in vitro, IFN-γ repressed alveolar macrophage cathelicidin (p < 0.05; n = 3 healthy controls).
Data indicates that in sarcoidosis, cathelicidin expression is deficient and directly correlates with disease severity and deficient circulating vitD levels.
Results further suggest that despite normal 1, 25 vitD levels and normal VDR expression, repressive mechanisms (possibly involving IFN-γ) may play a role in reducing cathelicidin expression in sarcoidosis BAL cells.
Ali Kanchwala, No Financial Disclosure Information; No Product/Research Disclosure Information