Effect of Muscle Unloading, Reloading and Exercise on Inflammation during a Head-down Bed Rest

Abstract

Muscles are affected by unloading during head-down bed rests and by reloading through normal reambulation. This study investigated the effects of a 60 days head-down long-term bed rest with or without predefined exercise countermeasures on the development of an inflammatory reaction.

Blood samples were taken before, during and after bed rest in control and exercise groups of women. They were assayed for soluble ICAM-1, VCAM-1, E- and L-selectin, IL1β, IL6, TNFα and CRP as markers of inflammation with ELISA.

Head-down long-term bed rest induced plasma volume variations which had an impact on the concentrations of the inflammatory factors and led to data corrections for a reliable analysis of the results. None of the marker of inflammation, except IL6 in control group, showed a significant change from baseline during bed rest. The main results were obtained during recovery. VCAM-1 increased in all groups, ICAM-1, in the control group, and L-selectin, in the exercise group. Peaks of IL6 and CRP were observed on day 59 of bed rest for IL6 and on day 2 of recovery for CRP in the control group. Exercise during bed rest prevented the augmentation of IL6, CRP and ICAM-1. These results might suggest a shift towards pro-inflammatory conditions, prevented in part by exercises.

Key words

modified muscle use - rehabilitation methods - systemic markers of ­inflammation - microgravity conditions

• References

• 1 Akimoto T, Furudate M, Saitoh M, Sugiura K, Waku T, Akama T, Kono I. Increased plasma concentrations of intercellular adhesion molecule-1 after strenuous exercise associated with muscle damage. Eur J Appl Physiol 2002; 86: 185-190
• 2 Alkner BA, Tesch PA. Knee extensor and plantar flexor muscle size and function following 90 days of bed rest with or without resistance exercise. Eur J Appl Physiol 2004; 93: 294-305
• 3 Arinell K, Christensen K, Blanc S, Larsson A, Fröbert O. Effect of prolonged standardized bed rest on cystatin C and other markers of cardiovascular risk. BMC Physiol 2001; 11: 17
• 4 Berrahmoune H, Herberth B, Lamont JV, Lambert D, Blankenberg S, Tiret L, Fitzgerald PS, Siest G, Visvikis-Siest S. Association of classical and related inflammatory markers with high-sensitivity C-reactive protein in healthy individuals: results from the Stanislas cohort. Clin Chem Lab Med 2007; 45: 1339-1346
• 5 Booth FW, Criswell DS. Molecular events underlying skeletal muscle atrophy and the development of effective countermeasures. Int J Sports Med 1997; 18: S265-S269
• 6 Bosutti A, Malaponte G, Zanetti M, Castellino P, Heer M, Guarnieri G, Biolo G. Calorie restriction modulates inactivity-induced changes in the inflammatory markers C-reactive protein and pentraxin-3. J Clin Endocrinol Metab 2008; 93: 3226-3229
• 7 Cantini M, Massimino ML, Rapizzi E, Rossini K, Catani C, Dalla Libera L, Carraro U. Human satellite cell proliferation in vitro is regulated by autocrine secretion of IL-6 stimulated by a soluble factor(s) released by activated monocytes. Biochem Biophys Res Commun 1995; 216: 49-53
• 8 Chopard A, Lecunff M, Danger R, Lamirault G, Bihouee A, Teusan R, Jasmin BJ, Marini JF, Leger JJ. Large-scale mRNA analysis of female skeletal muscles during 60 days of bed rest with and without exercise or dietary protein supplementation as countermeasures. Physiol Genomics 2009; 38: 291-302
• 9 Cuniffe B, Hore JA, Whitcombe DM, Jones KP, Baker JS. Davies B. Time course of changes in immunoendocrine markers following an international rugby game. Eur J Appl Physiol 2010; 108: 113-122
• 10 Custaud MC, Belin de Chantemerle E, Blanc S, Gauquelin-Koch G, Gharib C. Régulation de la volémie au cours d’une simulation d’impesanteur de longue durée. Can J Physiol Pharmacol 2005; 83: 1147-1153
• 11 Demiot C, Dignat-George F, Fortrat JO, Sabatier F, Gharib C, Larina I, Gauquelin-Koch G, Hughson R, Custaud MC. WISE 2005: chronic bed rest impairs microcirculatory endothelium in women. Am J Physiol 2007; 293: H3159-H3164
• 12 Dill DB, Costill DL. Calculation of percentage changes in volumes of blood, plasma, and red cells in dehydration. J Appl Physiol 1974; 37: 247-248
• 13 Dorfman TA, Levine BD, Tillery T, Peshock RM, Hastings JL, Schneider SM, Macias BR, Biolo G, Hargens AR. Cardiac atrophy in women following bed rest. J Appl Physiol 2007; 103: 8-16
• 14 Edgell H, Zuj KA, Greaves DK, Shoemaker JK, Custaud MA, Kerbeci P, Arbeille P, Hughson RL. WISE-2005: adrenergic response of women following 56-days, 6 degrees head-down bed rest with or without exercise countermeasures. Am J Physiol 2007; 293: R2343-R2352
• 15 Fauve RM, Hevin MB. Réactions inflammatoires et réactions immunitaires. In: Russo-Marie F, Peltier A, Polla B. eds. L’inflammation. Paris: John Libbey eurotext; 1998: 10-20
• 16 Fischer CP, Berntsen A, Perstrup LB, Eskildsen P, Pedersen BK. Plasma levels of interleukin-6 and C-reactive protein are associated with physical inactivity independent of obesity. Scand J Med Sci Sports 2007; 17: 580-587
• 17 Fitts RH, Riley DR, Widrick JJ. Microgravity and skeletal muscle. J Appl Physiol 2000; 89: 823-839
• 18 Frenette J, Cai B, Tidball JG. Complement activation promotes muscle inflammation during modified muscle use. Am J Pathol 2000; 156: 2103-2110
• 19 Frenette J, St-Pierre M, Côté CH, Mylona E, Pizza FX. Muscle impairment occurs rapidly and precedes inflammatory cell accumulation after mechanical loading. Am J Physiol 2002; 282: R351-R357
• 20 Gearing AJH, Newman W. Circulating adhesion molecules in disease. Immunology Today 1993; 14: 506-512
• 21 Guinet P, Schneider SM, Macias BR, Watenpaugh DE, Hughson RL, Pavy le Traon A, Bansard JY, Hargens AR. WISE 2005: effect of aerobic and resistive exercises on orthostatic tolerance during 60 days bed rest in women. Eur J Appl Physiol 2009; 106: 217-227
• 22 Harris DJ, Atkinson G. Update – ethical standards in sport and exercise science research. Int J Sports Med 2011; 32: 819-821
• 23 Huda R, Solanki DR, Mathru M. Inflammatory and redox responses to ischemia/reperfusion in human skeletal muscle. Clin Sci 2004; 107: 497-503
• 24 Lagrand WK, Niessen HWM, Nijmeijer R. Role for complement as an intermediate between C-reactive protein and intercellular adhesion molecule-1 expression. Circulation 2001; 104: E46
• 25 Madej A, Okopien B, Kowalski J, Haberka M, Herman ZS. Plasma concentrations of adhesion molecules and chemokines in patients with essential hypertension. Pharmacol rep 2005; 57: 878-881
• 26 Mattusch F, Dufaux B, Heine O, Mertens I, Rost R. Reduction of the plasma concentration of C-reactive protein following nine months of endurance training. Int J Sports Med 2000; 21: 21-24
• 27 Monga M, Macias B, Groppo E, Kostelec M, Hargens A. Renal stone risk in simulated microgravity environment: impact of treadmill exercise with lower body negative pressure. J Urol 2006; 176: 127-131
• 28 Mora S, Cook N, Buring JE, Ridker PM, Lee IM. Physical activity and reduced risk of cardiovascular events: potential mediating mechanisms. Circulation 2007; 116: 2110-2118
• 29 Nguyen HX, Tidball JG. Expression of a muscle-specific, nitric oxide synthase transgene prevents muscle membrane injury and reduces muscle inflammation during modified muscle use in mice. J Physiol 2003; 550: 347-356
• 30 Ostrowski K, Rohde T, Asp S, Schjerling P, Pedersen BK. Pro- and anti-inflammatory cytokine balance in strenuous exercise in humans. J Physiol 1999; 515: 287-291
• 31 Panagiotakos DB, Pitsavos Chrysohoou C, Kavouras S, Stefanadis C. The association between leisure-time physical activity and inflammatory and coagulation markers related to cardiovascular disease: the ATTICA study. Prev Med 2005; 40: 432-437
• 32 Pasceri V, Willerson JT, Yeh ETH. Direct proinflammatory effect of C-reactive protein on human endothelial cells. Circulation 2000; 102: 2165-2168
• 33 Pavy-Le Traon A, Heer M, Narici MV, Rittweger J, Vernikos J. From space to earth: advances in human physiology from 20 years of bed rest studies (1986-2006). Eur J Appl Physiol 2007; 101: 143-194
• 34 Pepys MB. C-reactive protein fifty years on. Lancet 1981; 21: 653-657
• 35 Petersen AM, Pedersen BK. The anti-inflammatory effect of exercise. J Appl Physiol 2005; 98: 1154-1162
• 36 Ponthieux A, Herbeth B, Droesch S, Haddy N, Lambert D, Visvikis S. Biological determinants of serum ICAM-1, E-selectin, P-selectin and L-selectin levels in healthy subjects: the Stanislas study. Atherosclerosis 2004; 172: 299-308
• 37 Salanova M, Schiffl G, Püttmann B, Schoser BG, Blottner D. Molecular biomarkers monitoring human skeletal muscle fibers and microvasculature following long-term bed rest with and without countermeasures. J Anat 2008; 212: 306-318
• 38 Shearer WT, Ochs HD, Lee BN, Cohen EN, Reuben JM, Cheng I, Thompson B, Butel JS, Blancher A, Abbal M, Aviles H, Sonnenfeld G. Immune responses in adult female volunteers during the bed-rest model of spaceflight: antibodies and cytokines. J Allergy Clin Immunol 2009; 123: 900-905
• 39 Shephard RJ. Adhesion molecules, catecholamines and leucocyte distribution during and following exercise. Sports Med 2003; 33: 261-284
• 40 Smith LL, Anwar A, Fragen M, Rananto C, Johnson R, Holbert D. Cytokines and cell adhesion molecules associated with high-intensity eccentric exercise. Eur J Appl Physiol 2000; 82: 61-67
• 41 Stowe RP, Sams CF, Pierson DL. Effects of mission duration on neuroimmune responses in astronauts. Aviat Space Environ Med 2003; 74: 1281-1284
• 42 Susuki K, Nakaji S, Yamada M, Totsuka M, Sato K, Sugawara K. Systemic inflammatory response to exhaustive exercise. Cytokine kinetics. Exerc Immunol Rev 2002; 8: 6-48
• 43 Tidball JG. Inflammatory processes in muscle injury and repair. Am J Physiol 2005; 288: R345-R353
• 44 Trappe S, Creer A, Slivka D, Minchev K, Trappe T. Single muscle fiber function with concurrent exercise or nutrition countermeasures during 60 days of bed rest in women. J Appl Physiol 2007; 103: 1242-1250
• 45 Trappe TA, Burd NA, Louis ES, Lee GA, Trappe SW. Influence of concurrent exercise or nutrition countermeasures on thigh and calf muscle size and function during 60 days of bed rest in women. Acta Physiol 2007; 191: 147-159
• 46 Vaporciyan A, Mulligan MS, Warren JS, Barton PA, Miyasaka M, Ward PA. Up-regulation of lung vascular ICAM-1 in rats is complement dependent. J Immunol 1995; 155: 1442-1449
• 47 Watenpaugh DE, Ballard RE, Schneider SM, Lee SMC, Ertl AC, William JM, Boda WL, Hutchinson KJ, Hargens AR. Supine lower body negative pressure exercise during bed rest maintains upright exercise capacity. J Appl Physiol 2000; 89: 218-227
• 48 Watters WW, Platts SH, Mitchell BM, Whitson PA, Meck JV. Plasma volume restoration with salt tablets and water after bed rest prevents orthostatic hypotension and changes in supine hemodynamic and endocrine variables. Am J Physiol 2005; 288: H839-H847
• 49 Winkelman C. Inactivity and inflammation: selected cytokines as biologic mediators in muscle dysfunction during critical illness. AACN Clin Issues 2004; 15: 74-82