These diseases can occur at any age, regardless of gender or origin. preventative measures. During inflammation, pro-inflammatory factors such as interleukins (IL)-6, -17, -21, -22, and -23 are secreted, while anti-inflammatory factors including IL-10 are downregulated. Research conducted over the past several years has focused on inhibiting inflammatory pathways and activating anti-inflammatory factors to improve the quality of life of people with rheumatic diseases. The aim of this paper is to review current knowledge on stimulatory and inhibitory pathways involving the signal transducer and activator of transcription 3 (STAT3). STAT3 has been shown to be one of the crucial factors involved in inflammation and is directly linked with other pro-inflammatory factors and thus is a target of current research on rheumatoid diseases. and by treatment with phosphodiesterase type 4 (PDE4) inhibitor (ibudilast) in activated RASFs. In addition, ibudilast also inhibited the expression and secretion of IL-12/23 p40, and Th17 cells responses KO mice. It was also shown that in RAW264.7 cells that do not express the RANKL, IL-21 promoted osteoclastogenesis regardless of the prevalence of RANKL (as suggested by previous studies). The osteoclastogenic potential is dependent on the PI3K/Akt signaling pathway, because the use of the PI3K/Akt pathway inhibitor (LY294002) significantly inhibited IL-21 induced osteoclastogenesis [97]. Interleukin-22 IL-22 is an -helical cytokine belonging to the IL-10 cytokine superfamily. The human gene is found on the 12q15 chromosome in addition to the and genes [98], and is produced by Th17 [56] and Th22 cells. The production of IL-22 is promoted by IL-17, IL-23, IL-1, aryl-hydrocarbon receptors (AhR), and Notch signaling [99]. The IL-22R is a complex of IL-22R1 and IL-10R2 containing an intracellular, transmembrane, and extracellular signaling region. The cytokine binds to IL-22R1 leading to the formation of a complex. The IL-22/IL-22R1 complex changes conformation and allows association of IL-10R2, initiating the activation of tyrosine kinases 2 (TYK2) and JAK1, followed by phosphorylation of STAT3 on the tyrosine and serine residues, STAT1 and STAT5. It is also an activator of the MAPK pathways (ERK1/2, MEK1/2, c-Jun N-terminal kinase (JNK), and p38 kinase), which ultimately leads to antibacterial and inflammatory processes as well as tissue repair, depending on the environment in the organism in which the cytokine is expressed [100]. There is data on the Alofanib (RPT835) duality of IL-22 activity in the literature which show the pro-inflammatory role of IL-22. On the other hand, there is also data on the protective role of IL-22 in controlling lung epithelial damage [101] or intestinal inflammation. ZKSCAN5 IL-22 levels are elevated in patients with rheumatoid arthritis and there is a relationship between its level and radiographic progression and disease activity [102, 103]. Researchers have shown that sulforaphane has an effect on increasing the levels of ROS in whole blood lymphocytes in RA patients. At the same time, reduced production of pro-inflammatory cytokines, i.e., IL-17A, IL-17F, and IL-22, has been demonstrated [69]. Studies conducted by Liu et al. [104] have shown that norepinephrine (NE), a neurotransmitter released from sympathetic nerves, inhibits the differentiation and function of Th17 cells by activating the 2-adrenergic receptor (2-AR) on CD4+ T lymphocytes. The studies were conducted on CIA mice. This suggests that NE may have anti-inflammatory effects in CIA. A study was also carried out on rats suffering from pristane induced arthritis (PIA). Increased cytokines produced by Th17 (IL-17A, IL-21, IL-22), mainly IL-22 in the ratio of Th1 cytokines (TNF-, INF-) and Th2 (IL-4, IL-10, TGF), have been shown in organs of immune rats (inguinal lymph nodes, spleen). Expression of IL-22 in synovium and serum correlated with the severity of PIA. The concentration of IL-21 was higher in PIA rats but was not significant compared to IL-22. In this study, IL-21 only supported Th17 differentiation and enhanced their response [99]. The same group showed that in PIA rats, the level of IL-22 expression was different in different phases of PIA. IL-22 levels increased in the spleen during the initial and chronic phase and Alofanib (RPT835) in the synovium in the chronic phase. In contrast, no elevated levels of IL-22 were found in the acute phase of inflammation. In the acute phase, an increase in IL-17F and IFN- expression was observed in the synovial membrane of PIA rats [105]. Zhong et al. [106] reports that elevated IL-22+ T cells and IL-22 can promote RA development. Targeting Th22 and Th17 Alofanib (RPT835) positively influences RA therapy. Patients were divided into two groups after basic treatments using conventional DMARDs, MTX, and leflunomide. The decreased plasma level of IL-22 correlated with a decreased level of Th22 and positively correlated with the reduction of DAS after treatment. The involvement of these cells in the pathogenesis of RA was previously demonstrated [107]. It has also been shown that treatment.