Effects of pentoxifylline on whole blood IL‐2 and IFN‐gamma gene expression in normal dogs

Abstract

Background Pentoxifylline (PTX) is a methylxanthine phosphodiesterase inhibitor that is used as a hemorrheologic and anti‐inflammatory agent in veterinary and human medicine. In human studies, PTX has been shown to decrease T‐cell production of cytokines such as IL‐2 and IFN‐γ. A RT‐qPCR assay to measure activated T‐cell gene expression of IL‐2 and IFN‐γ has been validated in dogs. Objectives The goal of this study was to utilize this assay to investigate the effects of PTX on in vitro cytokine gene expression in canine whole blood. Methods Whole blood from seven healthy dogs was collected and incubated with various concentrations of PTX for 1 hr before activation. PTX concentrations spanned and exceeded blood concentrations achieved when administered at clinically relevant dosages (1, 2, 10, 50 and 200 μg/ml). Cyclosporine was used at a concentration of 500 ng/ml as a positive control. All blood samples, including untreated activated baseline samples, were then activated with phorbol myristate acetate and ionomycin for 5 hrs. Results Analysis of activated whole blood by RT‐qPCR revealed that there was not a significant suppression of IL‐2 or IFN‐γ gene expression at any concentration of PTX when evaluating ΔCt values. All samples exposed to cyclosporine showed significant changes from untreated activated baseline samples, demonstrating marked suppression as the positive control. Cytokine expression, presented as a percentage of untreated activated baseline samples, was also evaluated. After exposure to the highest concentration of PTX (200 μg/ml), median percentage cytokine expression was suppressed to just below 50% of baseline values. This concentration, however, is much higher than blood concentrations reported to be achieved at standardly used pentoxifylline doses. Conclusions PTX does not appear to significantly suppress T‐cell cytokine production in samples from most dogs at clinically relevant drug concentrations. Further testing is needed to establish the full effects of PTX on the immune system in dogs.

Treatment with benznidazole and pentoxifylline regulates microRNA transcriptomic profile in a murine model of Chagas chronic cardiomyopathy

“…Thus, these data suggest that the production of proinflammatory cytokines, intrinsic to CD pathogenesis [57,79], might influence the upregulation of miR-146b-5p, as seen in our recent study [64]. Moreover, the downmodulation of miR-146b-5p upon Bz and Bz+PTX therapies might be due to the parasite clearance and/or the immunomodulatory effects previously reported individually for both Bz [66,68,69,80] and PTX [75,81,82]. Thus, this result opens a new venue for the further analysis of miR-146b-5p as a potential biomarker of cure in CD since the restored level of this miRNA occurred in parallel with parasite clearance after treatment and downregulation of inflammatory mediators, such as TNF/TNFR1 and NO/iNOS pathways, involved in CCC pathogenesis, as previously shown [25,26].…”

Successful management of feline pemphigus foliaceus with pentoxifylline and topical hydrocortisone aceponate

“…In addition, in order to avoid significant suppression of the Th1 immunity by conventional therapy and because of its efficacy in treatment of human pemphigus vulgaris, pentoxifylline was added (Kummari et al., 2020; Marsella & Nicklin, 2000; Takehana et al., 2002). Although not efficacious against FIP, it is known to be well tolerated in cats with FIP (Fischer et al., 2011).…”

The Use of Pentoxifylline Topical in the Treatment of Alopecia in Rats

“…This was also observed to impede the release of interferon (IFN)-g by leukocytes. By suppressing the production of pro-inflammatory mediators by keratinocytes and leukocytes, PTX may eliminate or decrease the initial stage of the inflammatory response 27 .…”