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Recombinant IL-4 aggravates experimental autoimmune uveoretinitis in rats
S Ramanathan1, Y de Kozak, A Saoudi
1INSERM Unit 430, Broussais Hospital, Paris, France.
Journal of Immunology (Baltimore, Md. : 1950)
|September 1, 1996
Summary
Interleukin-4 (IL-4) can worsen autoimmune eye disease (experimental autoimmune uveoretinitis) by increasing inflammatory cytokines like IFN-gamma. This suggests IL-4
Area of Science:
- Immunology
- Autoimmunity
- Ophthalmology
Background:
- Interleukin-4 (IL-4) typically promotes Th2 immune responses and can protect against Th1-dependent autoimmune diseases.
- The role of IL-4 in experimental autoimmune uveoretinitis (EAU), a Th1-dependent disease, was investigated.
Purpose of the Study:
- To determine the effect of IL-4 on the severity of EAU.
- To elucidate the mechanisms underlying IL-4's action in this Th1-dependent autoimmune model.
Main Methods:
- Lewis rats were immunized with soluble retinal antigen to induce EAU.
- Rats were treated with IL-4, and disease severity was assessed.
- Neutralizing anti-IL-4 antibodies were used to block IL-4 activity.
- Ex vivo analysis of cytokine production (IFN-gamma, TNF-alpha, nitric oxide) was performed.
- In vitro studies examined IL-4's effect on splenocyte cytokine production.
Main Results:
- IL-4 treatment exacerbated EAU severity in Lewis rats.
- Neutralizing anti-IL-4 antibodies attenuated the increased disease severity.
- IL-4 treatment enhanced the production of IFN-gamma, TNF-alpha, and nitric oxide ex vivo.
- In vitro, IL-4 demonstrated a dose-dependent effect on IFN-gamma production by splenocytes, enhancing it at low concentrations and inhibiting it at high concentrations.
Conclusions:
- IL-4 can exacerbate Th1-dependent autoimmune diseases like EAU under certain conditions.
- IL-4 can induce the production of IFN-gamma and other inflammatory cytokines.
- IL-4 exerts a dose-dependent, differential effect on immune responses and autoimmunity.