The effects of interleukin-10 depletion in vivo on the immune response to Porphyromonas gingivalis in a murine model.
BACKGROUND
The immune response to Porphyromonas gingivalis in the mouse abscess model is known to be dependent upon CD4 T-cell activation and the regulatory role of cytokines. The role of interleukin-10 (IL-10) in this mouse model was examined in vivo.


METHODS
One-week-old, female BALB/c mice were divided into 4 groups. Groups 1 and 2 were given intraperitoneal (i.p.) injections of phosphate buffered saline (PBS) weekly for 5 weeks. Group 3 was given an i.p. injection of rat immunoglobulin. Group 4 was injected with rat anti-IL-10 antibodies. At week 6, group 1 was sham-immunized with PBS, and groups 2, 3, and 4 were injected with P. gingivalis lipopolysaccharide (Pg-LPS) weekly for 2 weeks. One week after the final immunization, delayed-type hypersensitivity (DTH) was assessed by footpad swelling to Pg-LPS. The level of serum antibodies to Pg-LPS and IFN-gamma (IFN-gamma) was determined by enzyme-linked immunosorbent assay. Dorsal abscess formation induced by the injection of viable P. gingivalis was examined daily for 30 days.


RESULTS
The footpad swelling of the anti-IL-10-treated group (group 4) was significantly higher than that of groups 1 to 3. Similarly, the serum IFN-gamma level in group 4 was much higher than that of the other experimental groups. There was no significant difference in serum IgG antibodies to Pg-LPS in any of the experimental groups. However, the level of IgM antibodies in group 4 mice was significantly lower than that in groups 2 and 3. In addition, serum IgG1 was suppressed in group 4 mice, while IgG2a antibodies were raised. However, there was no difference observed between the levels of IgG2b and IgG3 antibodies in any group of mice. The lesions in sham-immunized mice (group 1) persisted for 30 days, and those in group 2 and 3 were undetected by day 18 and 20, respectively. In sharp contrast, lesions in group 4 had healed completely by day 13.


CONCLUSIONS
This study has shown that IL-10 depletion in vivo in P. gingivalis LPS-induced immune response in mice led to an elevated DTH response, an increase in serum IFN-gamma levels, and raised levels of IgG and IgG2a antibodies. Treatment with anti-IL-10 antibodies resulted in suppressed IgG1 and IgM responses and a more rapid healing of abscesses than in non-IL-10-depleted mice. These results suggest that IL-10 depletion in Pg-LPS-induced immune response in mice may lead to a Th1-like immune response and provide strong protection against a subsequent challenge with live P. gingivalis in an abscess model.
Herminajeng
E
E
Department of Oral Medicine, Faculty of Dentistry, Gadjah Mada University, Yogyakarta, Indonesia.
Sosroseno
W
W
Bird
P S
PS
Seymour
G J
GJ
D000038:Abscess / Q000276:immunology; D000704:Analysis of Variance; D000818:Animals; D000906:Antibodies / Q000008:administration & dosage; D000907:Antibodies, Bacterial / Q000097:blood; D016866:Bacteroidaceae Infections / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007136:Immunoglobulins / Q000008:administration & dosage; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000172:deficiency* / Q000276:immunology; D016018:Least-Squares Analysis; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016966:Porphyromonas gingivalis / Q000276:immunology*; D051381:Rats; D017192:Skin Diseases, Bacterial / Q000276:immunology; D012965:Sodium Chloride; D013223:Statistics as Topic; D018417:Th1 Cells / Q000276:immunology; D014945:Wound Healing
D000906:Antibodies; D000907:Antibodies, Bacterial; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007136:Immunoglobulins; D008070:Lipopolysaccharides; D016753:Interleukin-10; D012965:Sodium Chloride; D007371:Interferon-gamma