Impact of interleukin-6 receptor blockade on acute response to exercise on insulin sensitivity and muscle glucose uptake in patients with Rheumatoid Arthritis

• Grant number: 20/04877-8
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Effective date (Start): August 01, 2021
• Effective date (End): July 02, 2023
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Bruno Gualano
• Grantee: Ítalo Ribeiro Lemes
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Rheumatoid Arthritis (RA) is a chronic inflammatory disease that affects the joints, causing pain, edema, physical disability and poor quality of life. In addition, RA patients are at increased risk of developing cardiovascular disease (CVD) and premature death. The most effective pharmacological treatment is the use of biological agents that inhibit the action of specific substances, such as interleukin 6 (IL-6) and Tumor Necrosis Factors (TNF). Physical exercise is considered a first-line non-pharmacological treatment in RA, improving inflammatory and metabolic profile, functional capacity, fatigue and preventing the onset of CVD. There is evidence that IL-6, when secreted as a result of exercise, brings several benefits. However, there is no study investigating the interaction between biological IL-6 blocking agents and exercise on metabolic responses, such as insulin sensitivity and glucose uptake, in patients with RA. To answer this question, adult women (s 18 years old) diagnosed with RA (n = 30) and healthy (n = 15) controls will be recruited for an acute session of combined exercise (aerobic and resistance). RA patients will be divided into 2 groups, according to the pharmacological treatment (tocilizumab or anti-TNF). The acute responses of insulin sensitivity after an acute session of exercise will be assessed by the hyperinsulinemic euglycemic clamp, and the molecular pathways will be assessed by muscle biopsy and gene and protein expression analysis. Positron Emission Tomography-Magnetic Resonance Imaging (PET/MRI) will be performed to quantify skeletal muscle glucose uptake. Between group comparisons will be performed by repeated measures analysis, with group and time as fixed factors and participants as random factor. If necessary, Tukey post hoc test will be performed. Statistical significance will be set at 5%. (AU)

Scientific publications

(7)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

HISAMATSU, THALYSI M.; OLIVEIRA, CRYSTIAN B.; LIRA, FABIO S.; MORELHAO, PRISCILA K.; AZEVEDO, BRUNA R.; LEMES, ITALO R.; FRANCO, MARCIA R.; PINTO, RAFAEL Z.. Occupational Physical Activity Was Associated With Disability Levels at 6-Month Follow-Up of Patients With Chronic Nonspecific Low Back Pain: A Prospective Cohort Study. JOURNAL OF PHYSICAL ACTIVITY & HEALTH, v. 19, n. 6, p. 8-pg., 2022-06-01. (20/04877-8, 16/04113-2)

DA SILVA MARTINS, MICHAEL DOUGLAS; LEMES, ITALO RIBEIRO; ESPOSITO, ELEONORA; MORELHAO, PRISCILA KALIL; NARCISO, PEDRO HENRIQUE; FRANCO, MARCIA RODRIGUES; PINTO, RAFAEL ZAMBELLI. Association Between Domain-Specific Physical Activity and Chronic Low Back Pain in Community-Dwelling Older Adults: A Cross-Sectional Study. JOURNAL OF AGING AND PHYSICAL ACTIVITY, v. 31, n. 5, p. 8-pg., 2023-03-16. (20/04877-8, 18/21935-1)

GUALANO, BRUNO; SIECZKOWSKA, SOFIA M.; LEMES, ITALO RIBEIRO; DA SILVA, RAFAEL PIRES; PINTO, ANA J.; MAZZOLANI, BRUNA C.; SMAIRA, FABIANA I.; AIKAWA, NADIA E.; KUPA, LEONARD V. K.; PASOTO, SANDRA G.; et al. Physical Activity: A Strategy to Improve Antibody Response to a SARS-CoV-2 Vaccine Booster Dose in Patients With Autoimmune Rheumatic Diseases. JOURNAL OF PHYSICAL ACTIVITY & HEALTH, v. 20, n. 4, p. 6-pg., 2023-03-03. (17/23688-9, 19/14820-6, 17/13552-2, 15/26937-4, 15/03756-4, 20/04877-8, 19/14819-8, 19/15231-4)

SMAIRA, FABIANA INFANTE; MAZZOLANI, BRUNA CARUSO; LEMES, ITALO RIBEIRO; DA SILVA, RAFAEL PIRES; PINTO, ANA J.; SIECZKOWSKA, SOFIA M.; AIKAWA, NADIA E.; PASOTO, SANDRA G.; MEDEIROS-RIBEIRO, ANA C.; SAAD, CARLA G. S.; et al. No Associations Between Physical Activity and Immunogenicity in SARS-CoV-2 Seropositive Patients With Autoimmune Rheumatic Diseases Prior to and After Vaccination. JOURNAL OF PHYSICAL ACTIVITY & HEALTH, v. N/A, p. 4-pg., 2023-06-08. (17/23688-9, 19/14820-6, 17/13552-2, 15/26937-4, 15/03756-4, 20/04877-8, 19/14819-8, 19/15231-4)

BRITO, GISELE MENDES; LEITE DO PRADO, DANILO MARCELO; REZENDE, DIEGO AUGUSTO; NAGEM JANOT DE MATOS, LUCIANA DINIZ; LOTURCO, IRINEU; CAMPOS VIEIRA, MARCELO LUIZ; DE SA PINTO, ANA LUCIA; BOUGLEUX ALO, RODRIGO OTAVIO; ARAUJO DE ALBUQUERQUE, LORENA CHRISTINE; BIANCHINI, FLAVIA RIVA; et al. The utility of cardiopulmonary exercise testing in athletes and physically active individuals with or without persistent symptoms after COVID-19. FRONTIERS IN MEDICINE, v. 10, p. 9-pg., 2023-04-26. (17/13552-2, 18/19418-9, 20/04877-8, 15/26937-4)

GUALANO, BRUNO; BRITO, GISELE MENDES; PINTO, ANA JESSICA; LEMES, ITALO RIBEIRO; NAGEM JANOT MATOS, LUCIANA DINIZ; DE SA PINTO, ANA LUCIA; LOTURCO, IRINEU; SPORT-COVID-19, COALITION. High SARS-CoV-2 infection rate after resuming professional football in Sao Paulo, Brazil. BRITISH JOURNAL OF SPORTS MEDICINE, JUL 2021. (17/13552-2, 20/04877-8)

GUALANO, BRUNO; SAAD, CARLA G. S.; SIECZKOWSKA, SOFIA M.; LEMES, ITALO RIBEIRO; DA SILVA, RAFAEL PIRES; PINTO, ANA J.; MAZZOLANI, BRUNA C.; SMAIRA, FABIANA, I; GIL, SAULO; OLIVEIRA-JUNIOR, GERSIEL; et al. Effect of an exercise bout before the booster dose of an inactivated SARS-CoV-2 vaccine on immunogenicity in immunocompromised patients. Journal of Applied Physiology, v. 132, n. 3, p. 7-pg., 2022-03-01. (19/15231-4, 17/13552-2, 17/23688-9, 15/26937-4, 20/04877-8, 19/14820-6, 19/14819-8, 15/03756-4)