Non-redundant roles for interleukin-1 alpha and interleukin-1 beta 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-1 alpha, IL-1 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 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-1 alpha, or IL-1 beta.


RESULTS
Blocking the IL-1 receptor with IL-1RA or neutralizing IL-1 alpha or IL-1 beta with specific antibody dramatically suppressed IgG2 production (50% to 70%). Additionally IL-1 alpha did not compensate for neutralized IL-1 beta, and additional IL-1 beta did not compensate for neutralized IL-1 alpha, suggesting the 2 monokines have separate roles in promoting IgG2. Furthermore, combinations of anti-IL-1 alpha and anti-IL-1 beta were more inhibitory than either antibody alone, and IL-1 alpha and IL-1 beta 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-1 beta.


CONCLUSIONS
IL-1 alpha and IL-1 beta appear to have critical and non-redundant roles in the generation and regulation of potent IgG2 responses, which appear to be important in human responses to carbohydrate-bearing bacteria.
Ishihara
Y
Y
Clinical Research Center for Periodontal Diseases, School of Dentistry, Virginia Commonwealth University, Richmond, VA, USA.
Zhang
J B
JB
Fakher
M
M
Best
A M
AM
Schenkein
H A
HA
Barbour
S E
SE
Tew
J G
JG
D000328:Adult; D016976:Aggregatibacter actinomycetemcomitans / Q000276:immunology; D000704:Analysis of Variance; D000911:Antibodies, Monoclonal; D002241:Carbohydrates / Q000276:immunology; D002478:Cells, Cultured; D002908:Chronic Disease; D005786:Gene Expression Regulation; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D007375:Interleukin-1 / Q000097:blood / Q000235:genetics / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology; D009000:Monocytes / Q000378:metabolism; D015846:Monokines / Q000276:immunology; D010518:Periodontitis / Q000097:blood / Q000145:classification / Q000276:immunology*; D011043:Pokeweed Mitogens; D016966:Porphyromonas gingivalis / Q000276:immunology; D017472:Receptors, Interleukin-1 / Q000276:immunology; D011994:Recombinant Proteins; D013223:Statistics as Topic
D000911:Antibodies, Monoclonal; D002241:Carbohydrates; D007074:Immunoglobulin G; D007375:Interleukin-1; D015846:Monokines; D011043:Pokeweed Mitogens; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins