The kynurenine pathway (KP) is highly regulated in the immune system, where it promotes immunosuppression in response to infection or inflammation. Indoleamine 2,3-dioxygenase 1 (IDO1), the main enzyme of KP, has a broad spectrum of activity on immune cells regulation, controlling the balance between stimulation and suppression of the immune system at sites of local inflammation, relevant to a wide range of autoimmune and inflammatory diseases. Various autoimmune diseases, among them endocrinopathies, have been identified to date, but despite significant progress in their diagnosis and treatment, they are still associated with significant complications, morbidity, and mortality. The precise cellular and molecular mechanisms leading to the onset and development of autoimmune disease remain poorly clarified so far. In breaking of tolerance, the cells of the innate immunity provide a decisive microenvironment that regulates immune cells’ differentiation, leading to activation of adaptive immunity. The current review provided a comprehensive presentation of the known role of IDO1 and KP activation in the regulation of the innate and adaptive arms of the immune system. Significant attention has been paid to the immunoregulatory role of IDO1 in the most prevalent, organ-specific autoimmune endocrinopathies—type 1 diabetes mellitus (T1DM) and autoimmune thyroiditis.

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection, and it accounts for about half of the cases of acute kidney injury (AKI). Although sepsis is the most frequent cause of AKI in critically ill patients, its pathophysiological mechanisms are not well understood. Sepsis has the ability to modulate the function of cells belonging to the innate immune system. Increased activity of indoleamine 2,3-dioxygenase 1 (IDO1) and production of kynurenines are the major metabolic pathways utilized by innate immunity cells to maintain immunological tolerance. The activation of the kynurenine pathway (KP) plays a dual role in sepsis—in the early stage, the induction of IDO1 elicits strong proinflammatory effects that may lead to tissue damage and septic shock. Afterwards, depletion of tryptophan and production of kynurenines contribute to the development of immunosuppression that may cause the inability to overpower opportunistic infections. The presented review provides available data on the various interdependencies between elements of innate immunity and sepsis-induced AKI (SAKI) with particular emphasis on the immunomodulatory significance of KP in the above processes. We believe that KP activation may be one of the crucial, though underestimated, components of a deregulated host response to infection during SAKI.

Ischemia-reperfusion injury (IRI) is of the most common causes of acute kidney injury (AKI); nevertheless, the mechanisms responsible for both early kidney injury and the reparative phase are not fully recognised. The inflammatory response following ischemia is characterised by the crosstalk between cells belonging to the innate immune system—dendritic cells (DCs), macrophages, neutrophils, natural killer (NK) cells, and renal tubular epithelial cells (RTECs). A tough inflammatory response can damage the renal tissue; it may also have a protective effect leading to the repair after IRI. Indoleamine 2,3 dioxygenase 1 (IDO1), the principal enzyme of the kynurenine pathway (KP), has a broad spectrum of immunological activity from stimulation to immunosuppressive activity in inflamed areas. IDO1 expression occurs in cells of the innate immunity and RTECs during IRI, resulting in local tryptophan (TRP) depletion and generation of kynurenines, and both of these mechanisms contribute to the immunosuppressive effect. Nonetheless, it is unknown if the above mechanism can play a harmful or preventive role in IRI-induced AKI. Despite the scarcity of literature in this field, the current review attempts to present a possible role of IDO1 activation in the regulation of the innate immune system in IRI-induced AKI.

The kynurenine pathway (KP) of tryptophan degradation includes several compounds that reveal immunomodulatory properties. The present study aimed to investigate the alteration in KP metabolites in young women with autoimmune thyroiditis (AIT) and their associations with thyroid function. The thyroid function tests, antithyroid antibodies measurement and ultrasonography of the thyroid gland have been performed in 57 young women with AIT and 38 age-matched healthy controls. The serum levels of tryptophan, kynurenine (KYN) and its metabolites were determined, and the activity of KP enzymes was calculated indirectly as product-to-substrate ratios. KP was activated and dysregulated in AIT, along with significantly elevated levels of KYN and anthranilic acid (AA), at the expense of the reduction of kynurenic acid (KYNA), which was reflected by the increase in the AA/KYNA ratio (p < 0.001). In univariate and multiple regression analyses, peripheral deiodinase (SPINA-GD) activity in AIT was positively associated with KYNA, AA, and quinolinic acid (QA). The merger of AA, AA/KYNA ratio, QA and SPINA-GD exhibited the highest sensitivity and specificity to predict AIT (p < 0.001) in receiver operating characteristic (ROC) analysis. In conclusion, the serum KYN metabolite profile is dysregulated in young women with AIT and could serve as a new predictor of AIT risk.

Atherosclerosis is a major contributor to ischemic stroke. Carotid plaque instability is a critical determinant of cerebrovascular events, yet its identification remains challenging. One chemokine with well-documented proatherogenic properties is MCP-1, whose levels are elevated in patients with conditions such as hypertension, obesity, and atherosclerosis. This study evaluated the association between obesity, serum MCP-1 levels, and carotid plaque instability as determined by ultrasound gray-scale median (GSM) analysis in 77 patients who underwent carotid endarterectomy. Patients were classified by body mass index. Serum MCP-1 concentrations were measured using the enzyme-linked immunosorbent assay technique. Analyses were performed to explore relationships between clinical parameters, biochemical markers, and plaque stability. Increasing body weight was paralleled by higher MCP-1 levels and lower GSM values, indicative of unstable plaques. Moreover, logistic regression analysis identified MCP-1 as one of the independent predictors of plaque instability, particularly in overweight and hypertensive patients. These results indicate the potential usefulness of MCP-1 as a biomarker of carotid plaque instability, confirming the negative effect of obesity in promoting other known cardiovascular risk factors causing plaque instability in patients with carotid atherosclerosis.

Background: The purpose of the study was to determine whether the use of β-adrenoceptor antagonists (β-blockers) can affect metalloproteinase 2 (MMP-2) and its tissue inhibitor (TIMP-2) in patients with chronic kidney disease (CKD) on conservative treatment. Methods: The circulating MMP-2/TIMP-2 system, proinflammatory cytokines (tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), and the marker of oxidative stress—Cu/Zn superoxide dismutase (Cu/Zn SOD)—were measured in 23 CKD patients treated with β-blockers [β-blockers (+)] and in 27 CKD patients not receiving the above medication [β-blockers (−)]. Results: The levels of MMP-2, TIMP-2, and IL-6 were significantly lower in the β-blockers (+) than in the β-blockers (−) group, whereas Cu/Zn SOD concentrations were not affected by β-blocker use. There was a strong, independent association between MMP-2 and TIMP-2 in both analyzed patient groups. In the β-blockers (+) group, MMP-2 levels were indirectly related to the signs of inflammation, whereas in the β-blockers (−) group, the alterations in the MMP-2/TIMP-2 system were associated with the oxidative stress marker and CKD etiology. Conclusions: This study is the first to suggest that the use of β-blockers was associated with the reduction in IL-6 and the MMP-2/TIMP-2 system in CKD, providing a pharmacological rationale for the use of β-blockers to reduce inflammation and abnormal vascular remodeling in CKD.