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IL-41: A novel serum marker correlates with disease activity in patients with ankylosing spondylitis

Abd Ali BM, Sharquie IK, Gorial FI

Med J Malaysia, 2024 Nov;79(6):777-784.
PMID: 39614798

INTRODUCTION: Interleukin (IL)-41, a type of cytokine also known as Metrnl, is involved in the pathogenesis of various inflammatory and immune-related diseases. However, its role in Ankylosing Spondylitis (AS), a field yet to be explored, remains a mystery. This study therefore assesses the diagnostic utility of IL-41 in patients with AS and examines the correlations among IL-41 levels, disease activity, and patients' demographic and clinical data. Such novel insights could have significant implications for the diagnosis and management of AS.
MATERIALS AND METHODS: Eighty-eight patients diagnosed with AS were enrolled from the Rheumatology Unit at Baghdad Teaching Hospital. Participants were categorized into two groups based on disease status: inactive (n = 44) and active (n = 44). Additionally, 44 matched healthy individuals were included as controls. Comprehensive medical histories were obtained, including disease duration, body mass index, sex, and age. Laboratory parameters related to the disease-such as C-reactive protein, human leukocyte antigen (HLA-B27), and rheumatoid factor-were also measured. Serum IL-41 levels were quantified using an enzyme-linked immunosorbent assay.
RESULTS: The study revealed a significant difference in levels of IL-41 in patients with AS (17.721±0.705 ng/L) compared to controls (8.495±0.984 ng/L; P = 0.009). The mean serum IL-41 concentration was highest in the active group (23.037±5.268 ng/L), followed by the inactive group (12.411±1.672 ng/L; p = 0.001) and controls (8.495±0.984 ng/L). Serum IL-41 levels demonstrated strong validity for diagnosing AS, with a cutoff value of ≥ 9.35 ng/mL and an area under the curve of 0.991. The sensitivity, specificity, and accuracy were 97.7%, 79.5%, and 92.38%, respectively (p = 0.002).
CONCLUSIONS: IL-41 is a potential new diagnostic biomarker for AS and associated with patient's disease activity. These insights could potentially transform the way we diagnose and manage AS, offering new avenues for improved patient care and outcomes.

Matched MeSH terms: Interleukins/blood
Fulltext Blastocystis sp. in Irritable Bowel Syndrome (IBS)--Detection in Stool Aspirates during Colonoscopy

Ragavan ND, Kumar S, Chye TT, Mahadeva S, Shiaw-Hooi H

PLoS One, 2015;10(9):e0121173.
PMID: 26375823 DOI: 10.1371/journal.pone.0121173

Blastocystis is one of the most common gut parasites found in the intestinal tract of humans and animals. Its' association with IBS is controversial, possibly as a result of irregular shedding of parasites in stool and variation in stool detection. We aimed to screen for Blastocystis in colonic stool aspirate samples in adult patients with and without IBS undergoing colonoscopy for various indications and measure the interleukin levels (IL-8, IL-3 and IL-5). In addition to standard stool culture techniques, polymerase chain reaction (PCR) techniques were employed to detect and subtype Blastocystis. All the serum samples collected were subjected for ELISA studies to measure the interleukin levels (IL-8, IL-3 and IL-5). Among 109 (IBS n = 35 and non-IBS n = 74) adults, direct stool examination and culture of colonic aspirates were initially negative for Blastocystis. However, PCR analysis detected Blastocystis in 6 (17%) IBS and 4 (5.5%) non-IBS patients. In the six positive IBS patients by PCR method, subtype 3 was shown to be the most predominant (3/6: 50%) followed by subtype 4 (2/6; 33.3%) and subtype 5 (1/6; 16.6%). IL-8 levels were significantly elevated in the IBS Blasto group and IBS group (p<0.05) compared to non-IBS and non-IBS Blasto group. The level of IL-3 in were seen to be significantly higher in than IBS Blasto group and IBS group (p<0.05) compared to non-IBS. Meanwhile, the IL-5 levels were significantly higher in IBS Blasto group (p<0.05) compared to non-IBS and non-IBS Blasto group. This study implicates that detecting Blastosystis by PCR method using colonic aspirate samples during colonoscopy, suggests that this may be a better method for sample collection due to the parasite's irregular shedding in Blastocystis-infected stools. Patients with IBS infected with parasite showed an increase in the interleukin levels demonstrate that Blastocystis does have an effect in the immune system.

Matched MeSH terms: Interleukins/blood
Fulltext Interleukin-27 exhibited anti-inflammatory activity during Plasmodium berghei infection in mice

Fazalul Rahiman SS, Basir R, Talib H, Tie TH, Chuah YK, Jabbarzare M, et al.

Trop Biomed, 2013 Dec;30(4):663-80.
PMID: 24522137 MyJurnal

Interleukin-27 (IL-27) has a pleiotropic role either as a pro-inflammatory or anti-inflammatory cytokine in inflammatory related diseases. The role and involvement of IL-27 during malaria was investigated and the effects of modulating its release on the production of major inflammatory cytokines and the histopathological consequences in major affected organs during the infection were evaluated. Results showed that IL-27 concentration was significantly elevated throughout the infection but no positive correlation with the parasitaemia development observed. Augmentation of IL-27 significantly elevated the release of anti-inflammatory cytokine, IL-10 whereas antagonising and neutralising IL-27 produced the opposite. A significant elevation of pro-inflammatory cytokines (IFN-γ and IL-6) was also observed, both during augmentation and inhibition of IL-27. Thus, it is suggested that IL-27 exerts an anti-inflammatory activity in the Th1 type response by signalling the production of IL-10 during malaria. Histopathological examination showed sequestration of PRBC in the microvasculature of major organs in malarial mice. Other significant histopathological changes include hyperplasia and hypertrophy of the Kupffer cells in the liver, hyaline membrane formation in lung tissue, enlargement of the white and red pulp followed by the disappearance of germinal centre of the spleen, and tubular vacuolation of the kidney tissues. In conclusion, it is suggested that IL-27 may possibly acts as an anti-inflammatory cytokine during the infection. Modulation of its release produced a positive impact on inflammatory cytokine production during the infection, suggesting its potential in malaria immunotherapy, in which the host may benefit from its inhibition.

Matched MeSH terms: Interleukins/blood
Raised levels of Il-6, Il-17a, and Il-22 in fatal leptospirosis

Wan Yusoff WSY, Abdullah M, Sekawi Z, Amran F, Yuhana MY, Mohd Taib N, et al.

Eur J Clin Microbiol Infect Dis, 2019 Dec;38(12):2349-2353.
PMID: 31529307 DOI: 10.1007/s10096-019-03699-5

Clinical manifestations of leptospirosis range from mild, common cold-like illness, to a life-threatening condition. The host immune response has been hypothesized to play a major role in leptospirosis outcome. Increased levels of inflammatory mediators, such as cytokines, may promote tissue damage that lead to increased disease severity. The question is whether cytokines levels may predict the outcome of leptospirosis and guide patient management. This study aimed to assess the association between Th1-, Th2-, and Th17-related cytokines with the clinical outcome of patients with leptospirosis. Different cytokine levels were measured in fifty-two plasma samples of hospitalized patients diagnosed with leptospirosis in Malaysia (January 2016-December 2017). Patients were divided into two separate categories: survived (n = 40) and fatal outcome (n = 12). Nineteen plasma samples from healthy individuals were obtained as controls. Cytokine quantification was performed using Simple Plex™ assays from ProteinSimple (San Jose, CA, USA). Measurements were done in triplicate and statistical analysis was performed using GraphPad software and SPSS v20. IL-6 (p = 0.033), IL-17A (p = 0.022), and IL-22 (p = 0.046) were significantly elevated in fatal cases. IL-17A concentration (OR 1.115; 95% CI 1.010-1.231) appeared to be an independent predictor of fatality of leptospirosis. Significantly higher levels of TNF-α (p ≤ 0.0001), IL-6 (p ≤ 0.0001), IL-10 (p ≤ 0.0001), IL-12 (p ≤ 0.0001), IL17A (p ≤ 0.0001), and IL-18 (p ≤ 0.0001) were observed among leptospirosis patients in comparison with healthy controls. Our study shows that certain cytokine levels may serve as possible prognostic biomarkers in leptospirosis patients.

Matched MeSH terms: Interleukins/blood
Modelling the immunopathophysiology of Brucella melitensis and its lipopolysaccharide in mice infected via oral route of exposure

Osman AY, Kadir AA, Jesse FF, Saharee AA

Microb Pathog, 2019 Nov;136:103669.
PMID: 31445124 DOI: 10.1016/j.micpath.2019.103669

Brucella melitensis is one of the leading zoonotic pathogens with significant economic implications in animal industry worldwide. Lipopolysaccharide, however, remains by far the major virulence with substantial role in diseases pathogenesis. Nonetheless, the effect of B. melitensis and its lipopolysaccharide on immunopathophysiological aspects largely remains an enigma. This study examines the effect of B.melitensis and its lipopolysaccharide on immunopathophysiological parameters following experimental infection using mouse model. Eighty four (n = 84) mice, BALB/c, both sexes with equal gender distribution and 6-8 weeks-old were randomly assigned into three groups. Group 1-2 (n = 72) were orally inoculated with 0.4 mL containing 109 CFU/mL of B. melitensis and its LPS, respectively. Group 3 (n = 12) was challenged orally with phosphate buffered saline and served as a control group. Animals were observed for clinical signs, haematological and histopathological analysis for a period of 24 days post-infection. We hereby report that B.melitensis infected group demonstrated significant clinical signs and histopathological changes than LPS infected group. However, both infected groups showed elevated levels of interleukins (IL-1β and IL-6) and antibody levels (IgM and IgG) with varying degrees of predominance in LPS infected group than B. melitensis infected group. For hormone analysis, low levels of progesterone, estradiol and testosterone were observed in both B. melitensis and LPS groups throughout the study period. Moreover, in B. melitensis infected group, the organism was re-isolated from the organs and tissues of gastrointestinal, respiratory and reproductive systems thereby confirming the infection and transmission dynamics. This report is the first detailed investigation comparing the infection progression and host responses in relation to the immunopathophysiological aspects in a mouse model after oral inoculation with B. melitensis and its lipopolysaccharide.

Matched MeSH terms: Interleukins/blood
Immuno-pathophysiological responses of mouse model to experimental infection with Brucella melitensis and its lipopolysaccharides via intraperitoneal route

Osman AY, Abdullah FF, Kadir AA, Saharee AA

Microb Pathog, 2016 Nov;100:17-29.
PMID: 27591112 DOI: 10.1016/j.micpath.2016.08.019

Brucella melitensis is one of the major zoonotic pathogens with significant economic implications worldwide. The pathogenicity is complex and not always well understood. Lipopolysaccharide (LPS) remains the major virulent factor of B. melitensis and responsible for the mechanism by which the pathogen causes its deleterious effects. In this study, 84 mice of 6-8 weeks old of both sexes were divided equally into 3 groups; namely Brucella melitensis infected group, lipopolysaccharide (LPS) infected group and control group. The former two groups contained 36 mice each with equal gender distribution. The control group consisted of 12 mice only. Animals in B. melitensis infected group, a single inoculum of 0.4 ml containing 10(9) of B. melitensis were intraperitoneally challenged while animals in LPS group, a single dose of 0.4 ml containing LPS extracted from the B. melitensis were intraperitoneally inoculated. Animals in control group received intraperitoneally, a single dose of 0.4 ml phosphate buffered saline (PBS) of pH7. Animals that were infected intraperitoneally with B. melitensis demonstrated significant clinical presentation; gross and histo-pathological evidence than LPS infected group. However, both infected groups showed elevated levels of interleukins (IL-1β and IL6), antibody levels (IgM an IgG) as early as 3 days post-infection with predominance in LPS infected group. In contrast, low levels of sex related hormonal changes in which LPS infected group showed the least concentration were also detected throughout the experimental period. In conclusion, B. melitensis can be transmitted via gastrointestinal, respiratory and reproductive tract. Moreover, LPS stimulated significantly the innate and acquired immune system without significant systemic dysfunction, suggesting potentiality of the protective properties of this component as alternative vaccine for brucellosis infection.

Matched MeSH terms: Interleukins/blood
Fulltext CD3+CD4+gp130+ T Cells Are Associated With Worse Disease Activity in Systemic Lupus Erythematosus Patients

Mohd Shukri ND, Farah Izati A, Wan Ghazali WS, Che Hussin CM, Wong KK

Front Immunol, 2021;12:675250.
PMID: 34149710 DOI: 10.3389/fimmu.2021.675250

The receptors for IL-35, IL-12Rβ2 and gp130, have been implicated in the inflammatory pathophysiology of autoimmune diseases. In this study, we set out to investigate the serum IL-35 levels and the surface levels of IL-12Rβ2 and gp130 in CD3+CD4+, CD3+CD4─ and CD3─CD4─ lymphocyte subpopulations in systemic lupus erythematosus (SLE) patients (n=50) versus healthy controls (n=50). The potential T cell subsets associated with gp130 transcript (i.e. IL6ST) expression in CD4+ T cells of SLE patients was also examined in publicly-available gene expression profiling (GEP) datasets. Here, we report that serum IL-35 levels were significantly higher in SLE patients than healthy controls (p=0.038) but it was not associated with SLEDAI-2K scores. The proportions of IL-12Rβ2+ and gp130+ cells in SLE patients did not differ significantly with those of healthy controls in all lymphocyte subpopulations investigated. Essentially, higher SLEDAI-2K scores were positively correlated with increased proportion of gp130+ cells, but not IL-12Rβ2+ cells, on CD3+CD4+ T cells (r=0.425, p=0.002, q=0.016). Gene Set Enrichment Analysis (GSEA) of a GEP dataset of CD4+ T cells isolated from SLE patients (n=8; GSE4588) showed that IL6ST expression was positively associated with genes upregulated in CD4+ T cells vs myeloid or B cells (q<0.001). In an independent GEP dataset of CD4+ T cells isolated from SLE patients (n=9; GSE1057), IL6ST expression was induced upon anti-CD3 stimulation, and that Treg, TCM and CCR7+ T cells gene sets were significantly enriched (q<0.05) by genes highly correlated with IL6ST expression (n=92 genes; r>0.75 with IL6ST expression) upon anti-CD3 stimulation in these SLE patients. In conclusion, gp130 signaling in CD3+CD4+ T cell subsets may contribute to increased disease activity in SLE patients, and it represents a promising therapeutic target for inhibition in the disease.

Matched MeSH terms: Interleukins/blood
Young adult survivors of childhood acute lymphoblastic leukemia show evidence of chronic inflammation and cellular aging

Ariffin H, Azanan MS, Abd Ghafar SS, Oh L, Lau KH, Thirunavakarasu T, et al.

Cancer, 2017 Nov 01;123(21):4207-4214.
PMID: 28654149 DOI: 10.1002/cncr.30857

BACKGROUND: Large epidemiologic studies have reported the premature onset of age-related conditions, such as ischemic heart disease and diabetes mellitus, in childhood cancer survivors, decades earlier than in their peers. The authors investigated whether young adult survivors of childhood acute lymphoblastic leukemia (ALL) have a biologic phenotype of cellular ageing and chronic inflammation.
METHODS: Plasma inflammatory cytokines were measured using a cytometric bead array in 87 asymptomatic young adult survivors of childhood ALL (median age, 25 years; age range, 18-35 years) who attended annual follow-up clinic and compared with healthy, age-matched and sex-matched controls. Leukocyte telomere length (LTL) was measured using Southern blot analysis.
RESULTS: Survivors had significant elevation of plasma interleukin-2 (IL-2), IL-10, IL-17a, and high-sensitivity C-reactive protein levels (all P 0.8 mg/dL) was related to increased odds of having metabolic syndrome (odds ratio, 7.256; 95% confidence interval, 1.501-35.074). Survivors also had significantly shorter LTL compared with controls (median, 9866 vs 10,392 base pairs; P = .021). Compared with published data, LTL in survivors was similar to that in healthy individuals aged 20 years older. Survivors who received cranial irradiation had shorter LTL compared with those who had not (P = .013).
CONCLUSIONS: Asymptomatic young adult survivors of childhood ALL demonstrate a biologic profile of chronic inflammation and telomere attrition, consistent with an early onset of cellular processes that drive accelerated aging. These processes may explain the premature development of age-related chronic conditions in childhood cancer survivors. Understanding their molecular basis may facilitate targeted interventions to disrupt the accelerated aging process and its long-term impact on overall health. Cancer 2017;123:4207-4214. © 2017 American Cancer Society.

Matched MeSH terms: Interleukins/blood*
Fulltext Evaluation of the Protective Effect of Deoxyribonucleic Acid Vaccines Encoding Granule Antigen 2 and 5 Against Acute Toxoplasmosis in BALB/c Mice

Ching XT, Fong MY, Lau YL

Am J Trop Med Hyg, 2017 Jun;96(6):1441-1447.
PMID: 28719288 DOI: 10.4269/ajtmh.16-0548

AbstractToxoplasma gondii infects a broad range of warm-blooded hosts, including humans. Important clinical manifestations include encephalitis in immunocompromised patients as well as miscarriage and fetal damage during early pregnancy. Toxoplasma gondii dense granule antigen 2 and 5 (GRA2 and GRA5) are essential for parasitophorous vacuole development of the parasite. To evaluate the potential of GRA2 and GRA5 as recombinant DNA vaccine candidates, these antigens were cloned into eukaryotic expression vector (pcDNA 3.1C) and evaluated in vaccination experiments. Recombinant DNA vaccines constructed with genes encoding GRAs were validated in Chinese hamster ovary cells before evaluation using lethal challenge of the virulent T. gondii RH strain in BALB/c mice. The DNA vaccines of pcGRA2 and pcGRA5 elicited cellular-mediated immune response with significantly higher levels of interferon-gamma, interleukin-2 (IL-2), IL-4, and IL-10 (P < 0.05) compared with controls. A mixed T-helper cell 1 (Th1)/Th2 response was associated with slightly prolonged survival. These findings provide evidence that DNA vaccination with GRA2 and GRA5 is associated with Th1-like cell-mediated immune responses. It will be worthwhile to construct recombinant multiantigen combining full-length GRA2 or/and GRA5 with various antigenic proteins such as the surface antigens and rhoptry antigens to improve vaccination efficacy.

Matched MeSH terms: Interleukins/blood