title: Decreased interleukin-1 receptor antagonist response following moderate exercise in patients with colorectal carcinoma after primary treatment.
abstract: Clinical and experimental studies have shown that a moderately increased physical activity level may have beneficial effects in terms of exercise conditioning, resistance to infection and decreased relative risk of cancer. Modulation of the innate and adaptive components of the immune system with a shift of cytokines and their antagonists to a more pro- and less anti-inflammatory response was found to be a prominent feature in non-tumor patients and healthy volunteers. As quantitative data concerning the cytokine/antagonist response following exercise are not available for tumor patients, we compared the effects of a post-operative rehabilitation program with moderate exercise (ME) intensity (0.55-0.65 x maximal aerobic power) with a program with low exercise (LE) intensity (0.30-0.40 x maximal aerobic power) in patients with curatively treated colorectal carcinoma (UICC II and III) measuring pro- (IL-1beta, IL-6, tumour necrosis factor (TNF)) and anti-inflammatory cytokines (IL-1 receptor antagonist, sTNF receptors I and II). Twenty-three patients participated in this prospective trial, N = 13 in the ME group, N = 10 in the LE group. Exercise was performed daily 30-40 min for 2 weeks. Basal (circulating) and LPS-stimulated (phasic) cytokine and antagonist response was determined before exercise and after 1 and 2 weeks using appropriate ELISA tests. The LPS-stimulated interleukin-1 receptor antagonist (IL-1ra) response in the ME group gradually decreased from 31,532.6 (160.0-70,028.0) to 18,033.0 pg/ml (5040.0-52,570.0) after one and to 22,892.0 pg/ml (6376.0-34,726.0) after 2 weeks (P < 0.05) with a concomitant decrease of the corresponding IL-1ra/IL-6 and IL-1ra/IL-1beta ratio: 2.51-1.41 and 4.1-3.1, respectively. In contrast, in the LE group LPS-stimulated cytokines and antagonists did not significantly change during exercise. Circulating cytokines and antagonists remained unchanged in both groups. In providing quantitative data in patients with curatively-treated colorectal cancer, we demonstrated that a short-term rehabilitation program with moderate exercise leads to a decreased LPS-induced antagonist response with a shift to a more pro-inflammatory state (decreased antagonist/cytokine ratio). Whether this change of the phasic immune response to moderate exercise may be clinically beneficial (decreased rates of infection, relapses and/or second tumours) is possible, but has to be investigated in long-term studies.
authors.affiliation: Oncology Department, Rehaklinik Ob der Tauber der LVA Baden-Württemberg, Academic Teaching Hospital, University of Heidelberg, Bismarckstr. 31, D-97980 Bad Mergentheim, Germany. allgayer@reha-klinik-odt.de
authors.forename: Hubert
authors.initials: H
authors.lastname: Allgayer
authors.forename: Susanne
authors.initials: S
authors.lastname: Nicolaus
authors.forename: Stephan
authors.initials: S
authors.lastname: Schreiber
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology / Q000401:mortality / Q000534:rehabilitation* / Q000628:therapy; D000328:Adult; D000368:Aged; D017024:Chemotherapy, Adjuvant; D003082:Colectomy / Q000379:methods; D015179:Colorectal Neoplasms / Q000276:immunology / Q000401:mortality / Q000534:rehabilitation* / Q000628:therapy; D003131:Combined Modality Therapy; D016207:Cytokines / Q000032:analysis* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D015444:Exercise; D005260:Female; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D008297:Male; D008875:Middle Aged; D011336:Probability; D011379:Prognosis; D011446:Prospective Studies; D017472:Receptors, Interleukin-1 / Q000032:analysis* / Q000276:immunology; D018570:Risk Assessment; D012795:Sialoglycoproteins / Q000032:analysis* / Q000276:immunology; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D016207:Cytokines; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins