Methamphetamine use and HSV-1 coinfection synergistically alter IFNα, IFNγ, and IL-29 expression in gingival crevicular fluid: implications for gingivitis pathogenesis

Background. Methamphetamine use compromises both innate and adaptive immune responses, substantially reducing the body’s ability to combat pathogens and preserve mucosal integrity. This immunosuppression heightens susceptibility to opportunistic infections such as herpes simplex virus type 1 (HSV-1), promotes viral reactivation, disrupts the balance and diversity of the oral microbiota, and accelerates inflammatory processes within oral tissues. As a result, it exacerbates a wide range of oral health problems, including gingivitis, periodontal disease, dental caries, oral mucosal lesions, and delayed wound healing within the oral cavity. The aim of the study was to investigate the levels of interferon-alpha (IFNα), interferon-gamma (IFNγ), and interleukin-29 (IL-29) in methamphetamine users with or without HSV-1 infection, and to examine their association with the development of gingivitis. Materials and methods. This case-control study included 88 male participants aged 20–35 years, categorized into four groups: healthy controls, methamphetamine users, methamphetamine users with HSV-1 infection, and patients with gingivitis. Gingival crevicular fluid (GCF) samples were collected from all participants, and the concentrations of IFNα, IFNγ, and IL-29 were measured using enzyme-linked immunosorbent assay (ELISA). Results. IFNα and IFNγ levels were highest in the healthy control group and were significantly reduced in the methamphetamine, methamphetamine with HSV-1, and gingivitis groups (p 0.05). In contrast, IL-29 levels were significantly elevated in gingivitis patients compared to all other groups. Furthermore, methamphetamine users with HSV-1 infection exhibited markedly higher IL-29 concentrations than methamphetamine users without HSV-1 infection. Conclusion. Methamphetamine use and HSV-1 infection significantly impair immune cytokine responses, reflected by marked reductions in IFNα and IFNγ levels, alongside elevated IL-29. The pronounced increase in IL-29 was most evident in gingivitis patients, suggesting a potential role for this cytokine in amplifying local inflammatory processes and contributing to periodontal tissue breakdown.