We investigated whether
interleukin-4 (IL-4) is present and capable of reducing inflammatory changes seen in
ifosfamide-induced
hemorrhagic cystitis. Male Swiss mice were treated with saline or
ifosfamide alone or
ifosfamide with the classical protocol with
mesna and analyzed by changes in bladder wet weight (BWW), macroscopic and microscopic parameters, exudate, and
hemoglobin quantification. In other groups,
IL-4 was administered intraperitoneally 1 h before
ifosfamide. In other experimental groups, C57BL/6 WT (wild type) and C57BL/6 WT
IL-4 (-/-) knockout animals were treated with
ifosfamide and analyzed for changes in BWW. Quantification of bladder
IL-4 protein by ELISA in control,
ifosfamide-, and
mesna-treated groups was performed. Immunohistochemistry to
tumor necrosis factor-alpha (TNF-α) and
interleukin-1 beta (IL-1β) as well as
protein identification by Western blot assay for
inducible nitric oxide synthase (iNOS) and
cyclooxygenase-2 (COX-2) was carried out on
ifosfamide- and IL-4-treated animals. In other experimental groups, antiserum against
IL-4 was given 30 min before
ifosfamide. In IL-4-treated animals, the severity of
hemorrhagic cystitis was significantly milder than in animals treated with
ifosfamide only, an effect that was reverted with serum anti-IL-4. Moreover, knockout animals for
IL-4 (-/-) exhibit a worse degree of
inflammation when compared to C57BL/6 wild type. Exogenous
IL-4 also attenuated TNF-α, IL-1β, iNOS, and COX-2 expressions in
ifosfamide-treated bladders.
IL-4, an anti-inflammatory
cytokine, attenuates the
inflammation seen in
ifosfamide-induced
hemorrhagic cystitis.