Introduction of the interleukin-10 gene into mice inhibited bleomycin-induced lung injury in vivo

Abstract

Interleukin (IL)-10 has been shown to reduce many inflammatory reactions. We investigated the in vivo effects of IL-10 on a bleomycin-induced lung injury model. Hemagglutinating virus of Japan (HVJ)-liposomes containing a human IL-10 expression vector (hIL10-HVJ) or a balanced salt solution as a control (Cont-HVJ) was intraperitoneally injected into mice on day -3. This was followed by intratracheal instillation of bleomycin (0.8 mg/kg) on day 0. Myeloperoxidase activity of bronchoalveolar lavage fluid and tumor necrosis factor-alpha mRNA expression in bronchoalveolar lavage fluid cells on day 7 and hydroxyproline content of the whole lung on day 21 were inhibited significantly by hIL10-HVJ treatment. However, Cont-HVJ treatment could not suppress any of these parameters. We also examined the in vitro effects of IL-10 on the human lung fibroblast cell line WI-38. IL-10 significantly reduced constitutive and transforming growth factor-beta-stimulated type I collagen mRNA expression. However, IL-10 did not affect the proliferation of WI-38 cells induced by platelet-derived growth factor. These data suggested that exogenous IL-10 may be useful in the treatment of pulmonary fibrosis.

Transgenic Overexpression of Interleukin (IL)-10 in the Lung Causes Mucus Metaplasia, Tissue Inflammation, and Airway Remodeling via IL-13-dependent and -independent Pathways

“…This may be particularly relevant to the airway remodeling in asthma, the fibrosis in interstitial lung diseases such as silicosis, and the salivary gland scarring seen in Sjogren's syndrome. These studies do not, however, support the concept that IL-10 is anti-fibrotic, as has been proposed by other investigators (69). In circumstances where anti-fibrotic effects of IL-10 are seen, our data would suggest that the decrease in fibrosis is a result of the ability of IL-10 to diminish tissue inflammation and inflammation-induced injury and not direct effects of IL-10 on matrix deposition or structural cell proliferation.…”

Studies of Murine Schistosomiasis Reveal Interleukin–13 Blockade As A Treatment for Established and Progressive Liver Fibrosis

“…The contribution of IL-10 to fibrosis is much less clear, although several recent studies suggest that it may play an important regulatory role. 7,[44][45][46] Using a model of carbon tetrachloride-induced liver injury, Thompson et al demonstrated an increased fibrotic response in IL-10 -deficient mice. 47 We, however, failed to observe a similar response in schistosome-infected mice, because fibrosis was only variably affected by the absence of IL-10.…”

Interleukin-10 deficiency aggravates kidney inflammation and fibrosis in the unilateral ureteral obstruction mouse model

“…9 The role of IL-10 in fibrosis has been also reported in other organs such as lung, heart and pancreas fibrosis. [10][11][12] The underlying mechanism of antifibrotic effects of IL-10 remains unclear, but it has been suggested that IL-10 can suppress extracellular matrix synthesis and inhibit key inflammatory pathways such as NF-kB. [13][14][15] In the context of kidney, IL-10 has been reported to effectively suppress the progression of acute and chronic renal damage in vivo.…”