Although COVID-19 infection is an immunosuppressant disease, many immunosuppressant agents, such as pulse methylprednisolone (PMP), dexamethasone (DXM), and tocilizumab (TCZ), were used during the pandemic. Secondary infections in patients with COVID-19 have been reported recently. This study investigated these agents\' effects on secondary infections and outcomes in patients with COVID-19 in intensive care units (ICUs). This study was designed retrospectively, and all data were collected from the tertiary intensive care units of six hospitals between March 2020 and October 2021. All patients were divided into three groups: Group I [GI, PMP (-), DXM (-) and TCZ (-)], Group II [GII, PMP (+), DXM (+)], and Group III [GIII, PMP (+), DXM (+), TCZ (+)]. Demographic data, PaO/FiO2 ratio, laboratory parameters, culture results, and outcomes were recorded. To compare GI-GII and GI-GIII, propensity score matching (PSM) was used by matching 14 parameters. Four hundred twelve patients with COVID-19 in the ICU were included in the study. The number of patients with microorganisms ≥ 2 was 279 (67.7%). After PSM, in GII and GIII, the number of (+) tracheal cultures and (+) bloodstream cultures detected different microorganisms ≥ 2 during the ICU period, neuropathy, tracheotomized patients, duration of IMV, and length of ICU stay were significantly higher than GI. The mortality rate was similar in GI and GII, whereas it was significantly higher in GIII than in GI. The use of immunosuppressant agents in COVID-19 patients may lead to an increase in secondary infections. In addition, increased secondary infections may lead to prolonged ICU stay, prolonged IMV duration, and increased mortality.

UNASSIGNED: Aggregated forms of the amyloid-β (Aβ) peptides which form protofibrils and fibrils in the brain are signatures of Alzheimer\'s disease (AD). Aggregates are also recognized by microglia, which in early phases maybe protective and in later phases contribute to the pathology. We have identified several small molecules, decoys which interfere with Aβ oligomerization and induce other aggregation trajectories leading to aggregated macrostructures which are non-toxic.
UNASSIGNED: This study investigates whether the small-molecule decoys affect microglial activation in terms of cytokine secretion and phagocytosis of Aβ peptide.
UNASSIGNED: The effects of the decoys (NSC 69318, NSC 100873, NSC 16224) were analyzed in a model of human THP-1 monocytes differentiated to microglia-like cells. The cells were activated by Aβ40 and Aβ42 peptides, respectively, and after treatment with each decoy the secreted levels of pro-inflammatory cytokines and the Aβ phagocytosis were analyzed.
UNASSIGNED: NSC16224, which generates a double-stranded aggregate of thin protofibrils, was found to block Aβ40- and Aβ42-induced increase in microglial secretion of pro-inflammatory cytokines. NSC 69318, selective for neurotoxicity of Aβ42, and NSC 100873 did not significantly reduce the microglial activation in terms of cytokine secretion. The uptake of Aβ42 was not affected by anyone of the decoys.
UNASSIGNED: Our findings open the possibility that the molecular decoys of Aβ aggregation may block microglial activation by Aβ40 and Aβ42 in addition to blocking neurotoxicity as shown previously.

The interplay between immune components and the epithelium plays a crucial role in the development and progression of head and neck squamous cell carcinoma (HNSCC). Natural killer (NK) cells, one of the main tumor-killing immune cell populations, have received increasing attention in HNSCC immunotherapy. In this review, we explore the mechanism underlying the interplay between NK cells and HNSCC. A series of immune evasion strategies utilized by cancer cells restrict HNSCC infiltration of NK cells. Overcoming these limitations can fully exploit the antineoplastic potential of NK cells. We also investigated the tumor-killing efficacy of NK cell-based immunotherapies, immunotherapeutic strategies, and new results from clinical trials. Notably, cetuximab, the most essential component of NK cell-based immunotherapy, inhibits the epidermal growth factor receptor (EGFR) signaling pathway and activates the immune system in conjunction with NK cells, inducing innate effector functions and improving patient prognosis. In addition, we compiled information on other areas for the improvement of patient prognosis using anti-EGFR receptor-based monoclonal antibody drugs and the underlying mechanisms and prognoses of new immunotherapeutic strategies for the treatment of HNSCC.

Colorectal cancer (CRC) is a major health problem worldwide and is usually detected in advanced stages, although it is highly treatable with early detection. The aim of this study was to examine the serum levels of various cytokines involved in the pathogenesis of CRC. The study included 29 patients and 30 healthy volunteers. Blood samples were collected twice from the patient group, before and after surgery, and these samples were evaluated for interleukin (IL) 4, 10, 23r, 37, 38, 40 and interferon (IFN) gamma levels. The results showed that IL-4 and IL-38 levels were significantly lower in the preoperative serum samples of the patient group compared to the control group (p < 0.001 and p = 0.01, respectively), while IL-4, IL-10, IL-38 and IL-40 levels increased significantly in the postoperative period (p = 0.004, p = 0.02, p = 0.03 and p = 0.004, respectively). These findings may contribute to the development of immunotherapy agents in the treatment of CRC. However, comprehensive studies on larger patient groups are needed to fully understand the role of cytokines in CRC pathogenesis.

Ulcerative colitis has been associated with psychological distress and an aberrant immune response. The immunomodulatory role of systemic cytokines produced during experimental intestinal inflammation in tonic immobility (TI) defensive behavior remains unknown. The present study characterized the TI defensive behavior of guinea pigs subjected to colitis induction at the acute stage and after recovery from intestinal mucosa injury. Moreover, we investigated whether inflammatory mediators (tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-8, IL-10, and prostaglandins) act on the mesencephalic nucleus, periaqueductal gray matter (PAG). Colitis was induced in guinea pigs by intrarectal administration of acetic acid. The TI defensive behavior, histology, cytokine production, and expression of c-FOS, IBA-1, and cyclooxygenase (COX)-2 in PAG were evaluated. Colitis reduced the duration of TI episodes from the first day, persisting throughout the 7-day experimental period. Neuronal c-FOS immunoreactivity was augmented in both columns of the PAG (ventrolateral (vlPAG) and dorsal), but there were no changes in IBA-1 expression. Dexamethasone, infliximab, and parecoxib treatments increased the duration of TI episodes, suggesting a modulatory role of peripheral inflammatory mediators in this behavior. Immunoneutralization of TNF-α, IL-1β, and IL-8 in the vlPAG reversed all effects produced by colitis. In contrast, IL-10 neutralization further reduced the duration of TI episodes. Our results reveal that peripherally produced inflammatory mediators during colitis may modulate neuronal functioning in mesencephalic structures such as vlPAG.

The recent pandemic caused by the SARS-CoV-2 virus and the associated mental health complications have renewed scholarly interest in the relationship between viral infections and the development of mental illnesses, a topic that was extensively discussed in the previous century in the context of other viruses, such as influenza. The most probable and analyzable mechanism through which viruses influence the onset of mental illnesses is the inflammation they provoke. Both infections and mental illnesses share a common characteristic: an imbalance in inflammatory factors. In this study, we sought to analyze and compare cytokine profiles in individuals infected with viruses and those suffering from mental illnesses. The objective was to determine whether specific viral diseases can increase the risk of specific mental disorders and whether this risk can be predicted based on the cytokine profile of the viral disease. To this end, we reviewed existing literature, constructed cytokine profiles for various mental and viral diseases, and conducted comparative analyses. The collected data indicate that the risk of developing a specific mental illness cannot be determined solely based on cytokine profiles. However, it was observed that the combination of IL-8 and IL-10 is frequently associated with psychotic symptoms. Therefore, to assess the risk of mental disorders in infected patients, it is imperative to consider the type of virus, the mental complications commonly associated with it, the predominant cytokines to evaluate the risk of psychotic symptoms, and additional patient-specific risk factors.

Endometriosis is known to be a chronic, debilitating disease. The pathophysiological mechanisms of endometriosis development include local chronic inflammation and a certain degree of local immune deficit. We investigated the relationship between the endometriosis severity, IL-8, IL-10, BDNF, VEGF-A serum and tissue levels, patient-related pain, and physical activity in a cohort of 46 patients diagnosed with endometriosis who underwent surgery. The same panel of biomarkers was investigated in a control group of 44 reproductive-aged patients with non-endometriotic gynecological pathology who underwent surgical intervention. Our data show a high statistical significance between tissue expression of IL-8, IL-10, patient-related pain, and the severity of endometriosis. No relationship was identified between serum or tissue levels of VEGF-A and BDNF and the severity of endometriosis. These results validate the presence of local chronic inflammation and immune deficit, thereby creating, alongside other studies in the field, an opportunity for the development of innovative and personalized treatment approaches in endometriosis.

Children with obstructive sleep apnea (OSA) frequently experience chronic low-grade systemic inflammation, with the inflammasome playing a central role in OSA. This cross-sectional study evaluated the relationship between weight status, autonomic function, and systemic inflammation in a cohort of 55 children with OSA, predominantly boys (78%) with an average age of 7.4 ± 2.2 years and an apnea-hypopnea index of 14.12 ± 17.05 events/hour. Measurements were taken of body mass index (BMI), sleep heart-rate variability, morning circulatory levels of interleukin-1β, interleukin-1 receptor antagonist, and interleukin-6, and tumor necrosis factor-α, anthropometry, and polysomnography. Multiple linear regression modeling showed that an apnea-hypopnea index was significantly associated with BMI, the standard deviation of successive differences between normal-to-normal intervals during N3 sleep, and the proportion of normal-to-normal interval pairs differing by more than 50 ms during rapid-eye-movement sleep. A moderated mediation model revealed that interleukin-1 receptor antagonist levels mediated the association between BMI and interleukin-6 levels, with sympathovagal balance during N3 sleep and minimum blood oxygen saturation further moderating these relationships. This study highlights the complex relationships between BMI, polysomnographic parameters, sleep heart-rate-variability metrics, and inflammatory markers in children with OSA, underlining the importance of weight management in this context.

Over the last thirty years, substantial evidence has accumulated in support of the hypothesis that dysregulation of inflammatory processes plays a critical role in the pathophysiology of depression. This review traces the evolution of research supporting this link, discussing key findings from several major investigative fronts: Alterations in inflammatory markers associated with depression; Mood changes following the exogenous administration of inflammatory challenges; The anti-inflammatory properties of traditional antidepressants and the promising antidepressant effects of anti-inflammatory drugs. Additionally, it explores how inflammatory processes interact with specific brain regions and neurochemical systems to drive depressive pathology. A thorough analysis of the 100 most-cited experimental studies on the topic ensures a comprehensive, transparent and unbiased collection of references. This methodological approach offers a panoramic view of the inflammation-depression nexus, shedding light on the complexity of its mechanisms and their connections to psychiatric categorizations, symptoms, demographics, and life events. Synthesizing insights from this extensive research, the review presents an integrative model of the biological foundations of inflammation-associated depression. It posits that we have reached a critical juncture where the translation of this knowledge into personalized immunomodulatory treatments for depression is not just possible, but imperative.

Poor mastitis control favors intramammary infection (IMI), which always involves CNS. This study aimed to determine the relationships of IL-4, IL-6, and IL-10 in mastitis milk with concurrent infection, bacterial pathogens, SCC, and MDA, an oxidative stress marker. All mastitis quarters from five smallholder dairy farms were sampled aseptically before morning milking and again before afternoon milking for bacteriological identification using MALDI-TOF mass spectrometry. The samples with the concomitant infection between streptococci and CNS and their pairs of another sample from the quarters were selected. In addition, samples were randomly chosen to have a controlled single infection. IL-4, IL-6, and IL-10 were measured with ELISA kits. MDA was measured using HPLC, while SCC was measured using Fossomatic™ FC. The results from a repeated measure analysis showed that IL-4 positively correlated with SCC, while IL-6 showed a negative trend. IL-4 levels were highest in CNS infections and significantly higher than in non-infected or mixed infections (p < 0.05). The IL-6 level of the mixed bacteria was highest and showed a different trend from non-infection, and the quarter was infected with streptococcal bacteria. In conclusion, from a single infection, the streptococci and CNS quarter showed varied immune responses, including trendily higher IL-6 and IL-4.