Non-Redundant Roles for Interleukin-1α and Interleukin-1β in Regulating Human IgG2.

Background: Serum concentrations of immunoglobulin G2 (IgG2) are elevated in localized aggressive periodontitis (LAgP) patients, and secretory products of monocytes from LAgP patients enhance IgG2 responses of lymphocytes from healthy subjects. Furthermore, genes regulating production of interleukin (IL)-1 influence the risk for both aggressive periodontitis (AgP) and chronic periodontitis. These observations, and the fact that IgG2 dominates responses to carbohydrates from Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis, prompted the hypothesis that IL-1α, IL-1β, 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 were manipulated; and the effect on IgG2 production was monitored. Manipulations of IL-1 were accomplished by adding specific neutralizing monoclonal antibodies or recombinant IL-1RA, IL-1α, or IL-1β.

Results: Blocking the IL-1 receptor with IL-1RA or neutralizing IL-1α or IL-1β with specific antibody dramatically suppressed IgG2 production (50% to 70%). Additional IL-1α did not compensate for neutralized IL-1β, and additional IL-1β did not compensate for neutralized IL-1α, suggesting the 2 monokines have separate roles in promoting IgG2. Furthermore, combinations of anti-IL-1α and anti-IL-1β were more inhibitory than either antibody alone, and IL-1α and IL-1β in combination appeared to work additively in promoting IgG2. Moreover, PBL cultures from a group of LAgP patients with high IgG2 levels had elevated levels of IL-1β.

Conclusion: IL-1α and IL-1β appear to have critical and nonredundant roles in the generation and regulation of potent IgG2 responses, which appear to be important in human responses to carbohydrate-bearing bacteria. J Periodontol 2001;72:1332-1339.