IL-4 abrogates the inhibitory effect of IL-10 on the development of experimental allergic encephalomyelitis in SJL mice.
IL-10 and IL-4 were studied with respect to their capacity to inhibit experimental allergic encephalomyelitis (EAE) induced in SJL/J mice by immunization with the proteolipid protein peptide PLP139-151. Treatment with 2 micrograms IL-10/day from day 0 until day 12 delayed onset of disease and inhibited the severity of EAE. By contrast, a daily dose of 0.5 microgram IL-4 was ineffective. Instead of acting in a synergistic fashion, IL-4 even abrogated the inhibitory effect of IL-10. The effects of IL-10 and IL-4 treatment were largely consistent with the (lack of) ability of these cytokines to down-regulate the inflammatory response in brain tissue. Although IL-4 was ineffective in the inhibition of EAE, lymph node cells from IL-4-treated mice displayed a strongly inhibited peptide-specific IFN-gamma production. By contrast, IL-10, which was effective in inhibiting EAE, showed no significant inhibition of IFN-gamma at this level. Neither cytokine treatment resulted in detectable levels of peptide-specific IL-4. Indirect evidence for the activity of Th2 cells in vivo came from the observation that IL-10 inhibited the primary PLP139-151-specific IgG2a and IgG3 response in favor of IgG1, whereas IL-4 inhibited the primary antibody response to the peptide, regardless of subclass. The combination of IL-4 and IL-10 did not affect the subclass composition. The observation that IL-10-treated mice remained sensitive to re-induction of EAE is not in support of an important role of Th2 cells in regulating disease activity in this model of actively induced EAE.
Nagelkerken
L
L
Division of Immunological and infectious Diseases, TNO Prevention and Health, Leiden, The Netherlands.
Blauw
B
B
Tielemans
M
M
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000517:prevention & control*; D005260:Female; D016753:Interleukin-10 / Q000037:antagonists & inhibitors* / Q000627:therapeutic use*; D015847:Interleukin-4 / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D018991:Myelin Proteolipid Protein / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology; D013997:Time Factors
D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments; C435023:myelin proteolipid protein (139-151); D016753:Interleukin-10; D015847:Interleukin-4