Interleukin-10 in murine metal-induced systemic autoimmunity

Area of Science:

• Immunology
• Autoimmunity
• Toxicology

Background:

• Systemic autoimmune diseases have complex etiologies, with cytokines like interleukin-10 (IL-10) playing a significant role in immune response.
• Previous observations indicated increased IL-10 mRNA in resistant mice exposed to heavy metals, suggesting a regulatory role.
• Understanding IL-10's function is crucial for developing targeted therapies for autoimmune conditions.

Purpose of the Study:

• To investigate the regulatory effect of IL-10 on the induction and manifestation of heavy metal-induced systemic autoimmunity.
• To assess the role of IL-10 in resistance to mercury (Hg) and silver (Ag) induced autoimmunity.
• To evaluate the impact of IL-10 deficiency and recombinant IL-10 treatment on autoimmune markers.

Main Methods:

• Utilized IL-10 gene-targeted mutation in a heavy metal-resistant mouse strain (B6.129P2-Il10(tm1Cgn)/J).
• Administered recombinant IL-10 (rIL-10) to genetically susceptible A.SW mice during heavy metal induction.
• Monitored autoimmune responses including lymphoproliferation, autoantibody production (ANoA, ANA, antichromatin), and immune complex deposition.

Main Results:

• IL-10-deficient mice showed altered autoantibody profiles (no ANoA, higher ANA) and increased splenic weight and IgG1 compared to wild-type.
• Both IL-10-deficient and wild-type mice exhibited significant increases in serum IgE upon mercury exposure.
• Recombinant IL-10 treatment in susceptible mice reduced the development of ANoA, antichromatin antibodies, and serum IgE.

Conclusions:

• Interleukin-10 (IL-10) demonstrably suppresses several facets of mercury-induced autoimmunity (HgIA).
• However, IL-10 is not the sole determinant of resistance against heavy metal-induced autoimmunity.
• Peroral silver administration effectively mitigates spontaneous immune activation in IL-10-deficient mice.