Background: Theophylline is a dimethyl xanthine that inhibits inflammation. Zinc sulfate as a strong antioxidant is commonly prescribed in the treatment of male subfertility. This study aimed to investigate the effect of theophylline and Zinc sulfate co-administration on inhibiting inflammation in the seminal plasma of Asthenoteratozoospermic men. Methods: 120 asthenoteratozoospermic patients participated in a double-blind, randomized clinical trial study and were randomly divided into four groups: Placebo, theophylline (200 mg/day), theophylline (200 mg/day) + zinc sulfate (220 mg/day) and zinc sulfate (220 mg/day). After 3 months of Oral treatment, the seminal plasma level of Tumor Necrosis Factor (TNF-α), an inflammatory factor, and the level of anti-inflammatory factor, Interlukin-10 (IL-10), was analyzed using the Enzyme immunoassay (EIA) kit (R and D Systems, Minneapolis, USA) at the beginning of the trial and at the end of the treatment. Data were analyzed statistically using the Repeated measurements ANOVA and the means were considered significantly different at P<0.05. Results: The seminal plasma level of TNF-α reduced significantly in all three groups compared to the placebo group but this reduction was significantly higher in the theophylline + zinc sulfate group compared to the theophylline and zinc sulfate groups. The level of IL-10 in the seminal plasma increased significantly in all three groups compared to the placebo group but this increase was significantly higher in the theophylline + zinc sulfate group when compared to the theophylline and zinc sulfate groups. Conclusion: Co-administration of theophylline and zinc sulfate can reduce inflammation in the seminal plasma. Therefore, this drug combination can be prescribed in cases of male subfertility for inhibition of inflammation.
