IL-4 abrogates the inhibitory effect of IL-10 on the development of experimental allergic encephalomyelitis in SJL mice
article
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 μg 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 μg 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-γ production. By contrast, IL-10, which was effective in inhibiting EAE, showed no significant inhibition of IFN-γ at this level. Neither cytokine treatment resulted in detectable levels of peptide-specific IL-4. Indirect evidence for the activity of T(h)2 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 T(h)2 cells in regulating disease activity in this model of actively induced EAE.
Topics
Experimental autoimmune encephalomyelitisIFN-γIL-4ImmunomodulationMultiple sclerosisT(h)1T(h)2AnimalsAntibody FormationCell DifferentiationDown-RegulationEncephalomyelitis, Autoimmune, ExperimentalFemaleInterleukin-10Interleukin-4MiceMice, Inbred StrainsMyelin Proteolipid ProteinPeptide FragmentsTh2 CellsTime Factors
TNO Identifier
234050
ISSN
09538178
Source
International Immunology, 9(9), pp. 1243-1251.
Pages
1243-1251
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