Non-redundant roles for interleukin-1 alpha and interleukin-1 beta in regulating human IgG2

Background: Serum concentrations of immunoglobulin G2 (IgG2) are elevated i n localized aggressive periodontitis (LAgP) patients, and secretory product s of monocytes from LAgP patients enhance IgG2 responses of lymphocytes fro m healthy subjects. Furthermore, genes regulating production of interleukin (IL)-1 influence the risk for both aggressive periodontitis (AgP) and chro nic periodontitis. These observations, and the fact that IgG2 dominates res ponses to carbohydrates from Actinobacillus actinomycetemcomitans and Porph yromonas gingivalis, prompted the hypothesis that IL-1 alpha, IL-beta, and IL-RA may help regulate human IgG2 responses. Methods: Human peripheral blood leukocytes (PBL) were stimulated in culture with pokeweed mitogen (PWM); the levels of available IL-1 gene products we re manipulated; and the effect on IgG2 production was monitored. Manipulati ons of IL-1 were accomplished by adding specific neutralizing monoclonal an tibodies or recombinant IL-1RA, IL-1 alpha, or IL-1 beta. Results: Blocking the IL-1 receptor with IL-1RA or neutralizing IL-1 alpha or IL-beta with specific antibody dramatically suppressed IgG2 production ( 50% to 70%). Additional IL-1 a did not compensate for neutralized IL-1 beta , and additional IL-1 beta did not compensate for neutralized IL-I (x, sugg esting the 2 monokines have separate roles in promoting IgG2. Furthermore, combinations of anti-IL-1 alpha and anti-IL-1 beta were more inhibitory tha n either antibody alone, and IL-1 alpha and IL-1 beta in combination appear ed to work additively in promoting IgG2. Moreover, PBL cultures from a grou p of LAgP patients with high IgG2 levels had elevated levels of IL- P. Conclusion: IL-1 a and IL-1 P appear to have critical and nonredundant role s in the generation and regulation of potent IgG2 responses, which appear t o be important in human responses to carbohydrate-bearing bacteria.