Inhibition of IL-4/IL-13 does not enhance the efficacy of allergen immunotherapy in murine allergic airway inflammation.
BACKGROUND
Successful allergen-specific immunotherapy (SIT) is associated with reduced Th2 cytokine production and the induction of IL-10-producing regulatory T cells. To improve treatment efficacy, we investigated the impact of an IL-4/IL-13 inhibitor during SIT.


METHODS
BALB/c mice were sensitized intranasally with ovalbumin (OVA) for 4 weeks. Subsequently, they were subjected to intranasal SIT, with OVA being administered at doses increasing from 1 mug to 1 mg over 3 weeks with or without an IL-4/IL-13 inhibitor. Serum OVA-specific antibodies were measured and bronchoalveolar lavage (BAL) fluids were checked for airway eosinophilia. Subsequently, lung tissue was examined histologically for inflammatory infiltrates. Cytokines were detected in BAL fluids and spleen cell cultures. Furthermore, CD4 CD25 double-positive spleen T cells were checked for intracellular IL-10 production by flow cytometry.


RESULTS
OVA sensitization resulted in persistent IgE synthesis and an eosinophil-rich allergic airway inflammation combined with increased IL-4 and IL-5 levels. Therefore, intranasal SIT could efficiently reverse the allergic phenotype. This was associated with decreased IL-4 and IL-5 levels, and increased IL-10 levels in BAL fluids as well as increased amounts of IL-10-producing CD25+ regulatory T cells. However, mice treated with the IL-4/IL-13 inhibitor during SIT did not produce significantly different results .


CONCLUSIONS
The use of an IL-4/IL-13 inhibitor as an adjuvant for SIT did not enhance anti-allergic effects. Thus, the observed reversal of Th2 responses during SIT may not be the keystone for successful therapy, but rather other factors, e.g. IL-10-producing regulatory T cells, may be crucial.
Gogishvili
Tea
T
Department of Dermatology, University of Wurzburg, Wurzburg, Germany.
Hahn
Christian
C
Meinhard
Julia
J
Hohaus
Andreas
A
Erb
Klaus
K
Sebald
Walter
W
Bröcker
Eva B
EB
Grunewald
Susanne M
SM
D000281:Administration, Intranasal; D000818:Animals; D001249:Asthma / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D003888:Desensitization, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D004804:Eosinophils / Q000276:immunology; D005434:Flow Cytometry; D006967:Hypersensitivity / Q000517:prevention & control*; D007249:Inflammation / Q000517:prevention & control*; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D018793:Interleukin-13 / Q000037:antagonists & inhibitors*; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology / Q000378:metabolism; D015847:Interleukin-4 / Q000037:antagonists & inhibitors*; D008168:Lung / Q000166:cytology / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D018793:Interleukin-13; D053645:Interleukin-2 Receptor alpha Subunit; D016753:Interleukin-10; D015847:Interleukin-4; D010047:Ovalbumin