Background: Hemp seed oil and terpenes are emerging as a dietary supplement and complementary therapy for patients suffering from knee osteoarthritis (KOA). However, the mechanisms and effects induced by these molecules on inflammatory cytokines are not yet fully understood. The aim of this study was to evaluate the changes in the cytokine IL-1β, IL-1α, IL-2, IL-6, and TNF-α levels from two oral hemp seed oil-based dietary supplements, of which only one included the addition of terpenes, in a population of KOA patients. Methods: Sera from venous blood samples were collected from thirty-eight patients who were divided into two subgroups. The control group underwent a 45-day treatment with a dietary supplement containing only hemp seed oil, while the treatment group assumed a hemp seed oil and terpene-based dietary supplement for the same number of days. A Bio-Plex Human Cytokine assay was performed by a customized human cytokine five-plex panel for IL-1β, IL-1α, IL-2, IL-6, and TNF-α. Patients were evaluated before the beginning of the treatment (T0) and soon after it (T1). Results: No measurable levels of IL-2 and TNF-α were found in any of the subjects. Low levels of IL-1β were found, which were significantly decreased in the treatment group. No change in IL-1α levels was observed, while treated patients had a significant increase in IL-6 levels. Conclusions: Hemp seed oil and terpene treatment modified the IL-1β and IL-6 levels, counteracting KOA inflammation in this way. In this study, IL-6 revealed its new and alternative action, since it is traditionally known as a pro-inflammatory factor, but it recently has been found to have anti-inflammatory activity in the muscle-derived form, which is the one it assumes as a myokine when activated by terpenes.
