Differential Regulation of Group A Streptococcal Peptidoglycan- Polysaccharide (PG-APS)-Stimulated Macrophage Production of IL-1 by Rat Strains Susceptible and Resistant to PG-APS-Induced Arthritis

The magnitude of the response of rat macrophages to group A streptococcal cell wall peptidoglycan-polysaccharide (PG-APS) stimulation is strain-dependent. A comparison of IL-1 expression between macrophages from a PG-APS-resistant (BUF) and PG-APS-sensitive (LEW) rat strain revealed that while mRNA levels for IL-1α and IL-1β were equivalent for the two strains, supernatants from BUF macrophages were less potent than LEW supernatants at stimulating thymocyte proliferation and contained less immunoreactive IL-1α and IL-1β protein. BUF and LEW macrophages expressed nearly equivalent levels of IL-1 receptor antagonist (IL-1ra) mRNA and secreted IL-1ra protein in supernatants. The ratio of IL-1/IL-1ra produced by macrophages may influence susceptibility versus resistance to PG-APS and is strongly suggestive of a regulatory role for macrophages in the pathogenesis of PG-APS-induced arthritis.