Interleukin-6 cytokine: An overview of the immune regulation, immune dysregulation, and therapeutic approach.

Several studies have shown that interleukin 6 (IL-6) is a multifunctional cytokine with both pro-inflammatory and anti-inflammatory activity, depending on the immune response context. Macrophages are among several cells that secrete IL-6, which they express upon activation by antigens, subsequently inducing fever and production of acute-phase proteins from the liver. Moreover, IL-6 induces the final maturation of B cells into memory B cells and plasma cells as well as an adaptive role for short-term energy allocation. Activation of IL-6 receptors results in the intracellular activation of the JAK/STAT pathway with resultant production of inflammatory cytokines. Several mechanisms-controlled IL-6 expression, but aberrant production was shown to be crucial in the pathogenesis of many diseases, which include autoimmune and chronic inflammatory diseases. IL-6 in combination with transforming growth factor ß (TGF-ß) induced differentiation of naïve T cells to Th17 cells, which is the cornerstone in autoimmune diseases. Recently, IL-6 secretion was shown to form the backbone of hypercytokinemia seen in the Coronavirus disease 2019 (COVID-19)-associated hyperinflammation and multiorgan failure. There are two classes of approved IL-6 inhibitors: anti-IL-6 receptor monoclonal antibodies (e.g., tocilizumab) and anti-IL-6 monoclonal antibodies (i.e., siltuximab). These drugs have been evaluated in patients with rheumatoid arthritis, juvenile idiopathic arthritis, cytokine release syndrome, and COVID-19 who have systemic inflammation. JAK/STAT pathway blockers were also successfully used in dampening IL-6 signal transduction. A better understanding of different mechanisms that modulate IL-6 expression will provide the much-needed solution with excellent safety and efficacy profiles for the treatment of autoimmune and inflammatory diseases in which IL-6 derives their pathogenesis.

Humoral immunological kinetics of severe acute respiratory syndrome coronavirus 2 infection and diagnostic performance of serological assays for coronavirus disease 2019: an analysis of global reports.

As the coronavirus disease 2019 (COVID-19) pandemic continues to rise and second waves are reported in some countries, serological test kits and strips are being considered to scale up an adequate laboratory response. This study provides an update on the kinetics of humoral immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and performance characteristics of serological protocols (lateral flow assay [LFA], chemiluminescence immunoassay [CLIA] and ELISA) used for evaluations of recent and past SARS-CoV-2 infection. A thorough and comprehensive review of suitable and eligible full-text articles was performed on PubMed, Scopus, Web of Science, Wordometer and medRxiv from 10 January to 16 July 2020. These articles were searched using the Medical Subject Headings terms 'COVID-19', 'Serological assay', 'Laboratory Diagnosis', 'Performance characteristics', 'POCT', 'LFA', 'CLIA', 'ELISA' and 'SARS-CoV-2'. Data from original research articles on SARS-CoV-2 antibody detection ≥second day postinfection were included in this study. In total, there were 7938 published articles on humoral immune response and laboratory diagnosis of COVID-19. Of these, 74 were included in this study. The detection, peak and decline period of blood anti-SARS-CoV-2 IgM, IgG and total antibodies for point-of-care testing (POCT), ELISA and CLIA vary widely. The most promising of these assays for POCT detected anti-SARS-CoV-2 at day 3 postinfection and peaked on the 15th day; ELISA products detected anti-SARS-CoV-2 IgM and IgG at days 2 and 6 then peaked on the eighth day; and the most promising CLIA product detected anti-SARS-CoV-2 at day 1 and peaked on the 30th day. The most promising LFA, ELISA and CLIA that had the best performance characteristics were those targeting total SARS-CoV-2 antibodies followed by those targeting anti-SARS-CoV-2 IgG then IgM. Essentially, the CLIA-based SARS-CoV-2 tests had the best performance characteristics, followed by ELISA then POCT. Given the varied performance characteristics of all the serological assays, there is a need to continuously improve their detection thresholds, as well as to monitor and re-evaluate their performances to assure their significance and applicability for COVID-19 clinical and epidemiological purposes.

Features and roles of T helper 22 cells in immunological diseases and malignancies.

T helper 22 (Th22) cell populations are a newly identified subset of CD4+  T cells that primarily mediate biological effects on the epithelial barrier through interleukin (IL)-22. Although, new studies showed that both Th22 and IL-22 are closely associated with the pathogenesis of inflammatory, autoimmune and allergic disease as well as malignancies. In this review, we aim to describe the development and characteristics of Th22 cells as well as their roles in the immunopathogenesis of immune-related disorders and cancer.

Sero-epidemiology of human T-cell lymphotropic viruses-1 and -2 infection among pregnant women attending Abuja Teaching Hospital, Nigeria.

BACKGROUND: There is the paucity of HTLV-1/-2 studies on Nigerian pregnant women despite the medical and public health significance of maternal-to-child transmission of HTLV-1/-2. OBJECTIVE: This study aims to determine the seroprevalence and risk factors of HTLV-1/-2 infections among pregnant women attending the University of Abuja Teaching Hospital (UATH), Abuja, Nigeria. MATERIALS AND METHODS: Blood samples were collected from consented pregnant women and analysed for ant-HTLV-1/-2 total antibodies using a commercial Enzyme-Linked Immunosorbent Assay (ELISA) kit. Pretested structured questionnaires were used to collate participants' socio-demographic variables and risk factors of HTLV infection. RESULTS: Out of the 156 pregnant women tested for HTLV-1/-2 antibodies, 16 (10.3%) were seropositive. There was no significant association between the socio-demographic variables collated and seroprevalence of HTLV-1/-2 infection among pregnant women (p> 0.05). Pregnant women with HIV infection had a lower prevalence of HLTV-1/-2 infection than those without HIV infections (7.5% versus 11.7%). Pregnant women with multiple sexual partners had a higher risk of HTLV-1/-2 infection than those who had single (OR = 2.08, 95% CI: 0.53-8.18). Women with a history of needles injury had a higher risk of HTLV-1/-2 infection than those who do not (OR = 1.24, 95% CI: 0.38-4.08). The history of blood transfusion was significantly associated with HTLV-1/-2 infection (p= 0.027). However, no significant association existed between other risk factors of HTLV-1/-2 infection among pregnant women (p> 0.05). CONCLUSION: Considering the 3% pooled national prevalence of HTLV-1/-2 infection in Nigeria, the seroprevalence reported in this study is relatively high. Thus, there is a need for more large cohort studies and routine screening of population at increased risk of infection.

Coronavirus disease 2019 (COVID-19): An overview of the immunopathology, serological diagnosis and management.

SARS-CoV-2 is a novel human coronavirus responsible for the Coronavirus disease 2019 (COVID-19) pandemic. Pneumonia and acute respiratory distress syndrome are the major complications of COVID-19. SARS-CoV-2 infection can activate innate and adaptive immune responses and result in massive inflammatory responses later in the disease. These uncontrolled inflammatory responses may lead to local and systemic tissue damage. In patients with severe COVID-19, eosinopenia and lymphopenia with a severe reduction in the frequency of CD4+ and CD8+ T cells, B cells and natural killer (NK) cells are a common feature. COVID-19 severity hinges on the development of cytokine storm characterized by elevated serum levels of pro-inflammatory cytokines. Moreover, IgG-, IgM- and IgA-specific antibodies against SARS-CoV-2 can be detected in most patients, along with the viral RNA, forming the basis for assays that aid in patient diagnosis. Elucidating the immunopathological outcomes due to COVID-19 could provide potential targets for immunotherapy and are important for choosing the best clinical management by consultants. Currently, along with standard supportive care, therapeutic approaches to COVID-19 treatment involve the use of antiviral agents that interfere with the SARS-CoV-2 lifecycle to prevent further viral replication and utilizing immunomodulators to dampen the immune system in order to prevent cytokine storm and tissue damage. While current therapeutic options vary in efficacy, there are several molecules that were either shown to be effective against other viruses such as HIV or show promise in vitro that could be added to the growing arsenal of agents used to control COVID-19 severity and spread.

Leucocytes and Th-associated Cytokine Profile of HIV-Leishmaniasis Co-Infected Persons Attending Abuja Teaching Hospital, Nigeria.

OBJECTIVE: T-helper cells (Th)-1& -2 cytokines homeostasis control or predict clinical outcome of infected persons, especially those with HIV /AIDS. This case-control study evaluated the leucocytes differentials, TNF-alpha, interleukin (IL)-2 and -10 levels among HIV infected persons with serological evidence of leishmaniasis attending University of Abuja Teaching Hospital, Nigeria. MATERIALS AND METHODS: Blood samples from 28 HIV infected persons who had Leishmania donovani rK39 and Immunoglobulin-G (IgG) positive (group 1), 30 age- & -sex matched HIV infected persons without Leishmania antibodies (group 2) and 30 apparently healthy persons without HIV and Leishmania antibodies (group 3). Full blood counts, TNF alpha, IL-2 and -10 levels were analyzed using automated hematology analyzer and ELISA, respectively. Structured questionnaires were used to collate biodata and clinical presentations of participants. RESULTS: Ten (35.7%) participants in group 1 were on ART, 15 (50%) in group 2 were on ART, while group 3 were ART naïve. There were significantly higher values in basophil (4.4±2.5%) and eosinophil counts (12.9±3.8%) in HIV/leishmania coinfected persons (p<0.005). However, other white cells subpopulation was significantly lower in HIV/leishmania co-infected participants (p<0.05). There was significantly reduced CD4+ T cell counts ([119±26 versus 348±63 versus 605±116 cells/mm3]), TNF-alpha ([36.82±8.21 versus 64.67±12.54 versus 254.98±65.59 pg/mL]) and IL-2 levels ([142.14±20.91 versus 507.6±84.42 versus 486.62±167.87 pg/mL]) among HIV/Leishmania co-infected participants compared to group 2 and group 3 participants, respectively. However, higher IL-10 level (80.35±14.57 pg/mL) was found in HIV/Leishmania co-infected participants as opposed to the HIV monoinfected (62.2±10.43 pg/mL) and apparently healthy persons (23.97±4.88 pg/mL) (p<0.001). CONCLUSION: Eosinophil, basophil counts and serum IL-10 level were high in HIV/Leishmania coinfected persons, demonstrating parasite-induced hypersensitivity and immunosuppression.