The potential of IFN-λ, IL-32γ, IL-6, and IL-22 as safeguards against human viruses: a systematic review and a meta-analysis

Abstract

Many studies have investigated the antiviral activity of cytokines, including interleukin-6 (IL-6), interleukin-22 (IL-22), interleukin-32 gamma (IL-32γ), and interferon-lambda (IFN-λ) in diverse populations. This study aims to evaluate the role of these cytokines in inhibition of various human and animal viruses when administered exogenously. A comprehensive meta-analysis and systematic review were conducted on all the relevant studies from three databases. Standard mean differences (SMDs) of overall viral inhibition were used to generate the difference in the antiviral efficacy of these cytokines between control and experimental groups. A total of 4,618 abstracts for IL-6, 3,517 abstracts for IL-22, 2,160 abstracts for IL-32γ, and 1,026 abstracts for IFN-λ were identified, and 7, 4, 8, and 35 studies were included, respectively, for each cytokine. IFN-λ (SMD = 0.9540; 95% CI: 0.69-0.22) and IL-32γ (SMD = 0.459; 95% CI: 0.02-0.90) showed the highest influence followed by IL-6 (SMD = 0.456; CI: -0.04-0.95) and IL-22 (SMD = 0.244; 95% CI: -0.33-0.81). None of the cytokines represented heterogeneity (tau² > 0), but only IFN-λ indicated the funnel plot asymmetry (p = 0.0097). Results also indicated that IFN-λ and IL-32γ are more potent antivirals than IL-6 and IL-22. The collective findings of this study emphasize that exogenously administered pro-inflammatory cytokines, specifically IFN-λ and IL-32, exhibit a significant antiviral activity, thereby underscoring them as potent antiviral agents. Nonetheless, additional research is required to ascertain their clinical utility and potential for integration into combinatorial therapeutic regimens against viral infections.

Keywords: antiviral; interferon-lambda; interleukin-22; interleukin-32 gamma; interleukin-6.

Figure 1

Flow diagram of study selection. Only research articles’ titles with the keywords (mentioned in methods) were selected for abstract reading. The relevant abstracts were included after duplication removal. Accessible full texts were screened and included. Full texts lacking exogenous cytokine treatment against viruses, mean viral titters with SEM, and number of replicates were excluded. (A–D) Study selection steps of IL-32, IFN-λ, IL-6, and IL-22, respectively.

Figure 2

Forest plot illustrating antiviral response of IFN-λ according to the estimated effect sizes. The vertical line on the zero represents null hypothesis; the length of horizontal lines represents the total effect size of each study, starting with a lower limit and ending on an upper limit; and the squares are the mean differences. The antiviral effect IFN-λ is rated on a scale of 0 to 5. Square positioned above “0” is considered antiviral effect of IFN-λ, whereas a square lying below “0” will favor its proviral role.

Figure 3

Forest plot illustrating antiviral response of IL-32γ according to the estimated effect sizes. The vertical line on the zero represents null hypothesis, the length of horizontal lines represents the total effect size of each study, starting with a lower limit and ending on an upper limit and the squares are the mean differences. The antiviral effect IL-32γ is rated on a scale of 0 to 5. Square positioned above “0” is considered antiviral effect of IL-32γ, whereas a square lying below “0” will favor its proviral role.

Figure 4

Forest plot illustrating antiviral response of IL-6 according to the estimated effect sizes. The vertical line on the zero represents null hypothesis; the length of horizontal lines represents the total effect size of each study, starting with a lower limit and ending on an upper limit; and the squares are the mean differences. The antiviral effect IL-6 is rated on a scale of 0 to 5. Square positioned above “0” is considered antiviral effect of IL-6, whereas a square lying below “0” will favor its proviral role. Square positioned above “0” is considered antiviral effect of IL-6, whereas a square lying below “0” will favor its proviral role.

Figure 5

Forest plot illustrating antiviral response of IL-22 according to the estimated effect sizes. The vertical line on the zero represents null hypothesis; the length of horizontal lines represents the total effect size of each study, starting with a lower limit and ending on an upper limit; and the squares are the mean differences. The antiviral effect IL-22 is rated on a scale of 0 to 5. Square positioned above “0” is considered antiviral effect of IL-22, whereas a square lying below “0” will favor its proviral role. Square positioned above “0” is considered antiviral effect of IL-22, whereas a square lying below “0” will favor its proviral role.