Interleukin-4 Modulates the Inflammatory Response in Ifosfamide-Induced Hemorrhagic Cystitis

Abstract

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.

Prevention of 1-palmitoyl lysophosphatidylcholine-induced inflammation by polyunsaturated acyl lysophosphatidylcholine

“…Additionally, IL-4 and IL-10 could down-regulate the formation of NO by blocking the NF-kB activation pathway [43] and inhibiting the expression of iNOS [44], respectively, which could partially explain the negative effect of LPC20:4 and LPC22:6 on LPC16:0-induced NO formation. Furthermore, the decrease in LPC16:0-induced PGE 2 formation level might be partly from the inhibitory effect of IL-4 and IL-10 on COX-2 enzyme as reported previously [45][46][47][48]. Taken together, it was suggested that elevation of IL-4 and IL-10 levels also contributed to the anti-inflammatory action of LPC20:4 and LPC22:6 in LPC16:0-induced inflammation.…”

A MLST Clade 2 Clostridium difficile strain with a variant TcdB induces severe inflammatory and oxidative response associated with mucosal disruption

“…interleukin-1 beta (IL-1 ), and the inducible isoform of nitric oxide synthase (iNOS) in ileal loop tissue sections were done using a previously described streptavidine-biotinperoxidase method [35][36][37]. In this regard, TNF-and IL-1 are pro-inflammatory …”

IPSE, a Parasite-Derived, Host Immunomodulatory Infiltrin Protein, Alleviates Resiniferatoxin-Induced Bladder Pain

“…IPSE also features a nuclear localization sequence (NLS) which facilitates its entry into host cell nuclei and subsequent modulation of transcription [4,5]. Macedo et al have reported that administration of IL-4 to mice with ifosfamide-induced hemorrhagic cystitis alleviates bladder injury [6]. This led us to test IPSE in this model.…”