Journal of Clinical Immunology

, Volume 19, Issue 6, pp 414–421 | Cite as

Acute Phase Responses and Cytokine Secretion in Chronic Fatigue Syndrome

  • Joseph G. Cannon
  • Jonathan B. Angel
  • Richard W. Ball
  • Leslie W. Abad
  • Laura Fagioli
  • Anthony L. Komaroff
Article

Abstract

This study addresses the hypothesis that clinical manifestations of chronic fatigue syndrome (CFS) are due in part to abnormal production of or sensitivity to cytokines such as interleukin-1β (IL-1β) and IL-6 under basal conditions or in response to a particular physical stress: 15 min of exercise consisting of stepping up and down on a platform adjusted to the height of the patella. The study involved 10 CFS patients and 11 age-, sex-, and activity-matched controls: of these, 6 patients and 4 controls were tested in both the follicular and the luteal phases of the menstrual cycle, and the remainder were tested in only one phase, for a total of 31 experimental sessions. Prior to exercise, plasma concentrations of the acute phase reactant α2-macroglobulin were 29% higher in CFS patients (P < 0.008) compared to controls. Secretion of IL-6 was generally higher for CFS patients (~38%), however, this difference was statistically significant only if all values over a 3-day period were analyzed by repeated-measures ANOVA (P = 0.035). IL-6 secretion correlated with plasma α2-macroglobulin in control subjects at rest (R = 0.767, P = 0.001). Immediately after exercise, the CFS patients reported greater ratings of perceived exertion (P=0.027) compared to the healthy control subjects. Ratings of perceived exertion correlated with IL-1β secretion by cells from healthy control subjects (R = 0.603, P = 0.022), but not from CFS patients, and IL-1β secretion was not different between groups. Exercise induced a slight (<12%) but significant (P = 0.006) increase in IL-6 secretion, but the responses of the CFS patients were not different than controls. Furthermore, no significant exercise-induced changes in body temperature or plasma α2-macroglobulin were observed. These data indicate that under basal conditions, CFS is associated with increased IL-6 secretion which is manifested by chronically elevated plasma α2-macroglobulin concentrations. These modest differences suggest that cytokine dysregulation is not a singular or dominant factor in the pathogenesis of CFS.

Chronic fatigue syndrome acute phase responses 

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REFERENCES

  1. 1.
    Strober W: Immunological function in chronic fatigue syndrome. In The Chronic Fatigue Syndrome, SE Straus (ed). New York, Marcel Dekker, 1994, pp 207–237Google Scholar
  2. 2.
    Holmes GP, Kaplan JE, Gantz NM, Komaroff AL, Schonberger LB, Straus SE, Jones JF, Dubois RE, Cunningham-Rundles C, Pahwa S, Tosato G, Zegans LS, Purtilo DT, Brown N, Schooley RT, Brus I: Chronic fatigue syndrome: A working case definition. Ann Intern Med 108:387–389, 1988Google Scholar
  3. 3.
    Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A, Group ICS: The chronic fatigue syndrome: A comprehensive approach to its definition and study. Ann Intern Med 121:953–959, 1994Google Scholar
  4. 4.
    Curti BD, Urba WJ, Longo DL, Janik JE, Sharfman WH, Miller LL, Cizza G, Shimizu M, Oppenheim JJ, Alvord WG, Smith JW: Endocrine effects of IL-1α and β administered in a phase I trial to patients with advanced cancer. J Immunother 19:142–148, 1996Google Scholar
  5. 5.
    Spath-Schwalbe E, Hansen K, Schmidt F, Schrezenmeier H, Marshall L, Burger K, Fehm H, Born J: Acute effects of recombinant human interleukin-6 on endocrine and central nervous sleep functions in healthy men. J Clin Endo Metab 83:1573–1579, 1998Google Scholar
  6. 6.
    Cannon JG: Exercise and the acute phase response. In Exercise and Immune Function, L Hoffman-Goetz (ed). Boca Raton, CRC Press, 1996, pp 39–54Google Scholar
  7. 7.
    Cannon JG, Angel JB, Abad LW, Vannier E, Mileno MD, Fagioli L, Wolff SM, Komaroff AL: Interleukin-1β, interleukin-1 receptor antagonist and soluble interleukin-1 receptor type II secretion in chronic fatigue syndrome. J Clin Immunol 17:253–261, 1997Google Scholar
  8. 8.
    Cannon JG, Angel JB, Abad LW, O'Grady J, Lundgren N, Fagioli L, Komaroff AL: Hormonal influences on stress-induced neutrophil mobilization in health and chronic fatigue syndrome. J Clin Immunol 18:291–298, 1998Google Scholar
  9. 9.
    Paffenbarger RS, Hyde RT, Wing AL, Hsieh C-C: Physical activity, all-cause mortality and longevity of college alumni. N Engl J Med 314:605–613, 1986Google Scholar
  10. 10.
    Borg G: Perceived exertion as an indicator of somatic stress. Scand J Rehab Med 2–3:92–98, 1970Google Scholar
  11. 11.
    Barofsky I, Legro MW: Definition and measurement of fatigue. Rev Infect Dis 13(Suppl 1):S94-S97, 1991Google Scholar
  12. 12.
    Gauldie J, Baumann H: Cytokines and acute phase protein expression. In Cytokines and Inflammation, ES Kimball (ed). CRC Press, Boca Raton, 1991Google Scholar
  13. 13.
    Buchwald D, Wener MH, Pearlman T, Kith P: Markers of inflammation and immune activation in chronic fatigue and chronic fatigue syndrome. J Rheumatol 24:372–376, 1997Google Scholar
  14. 14.
    Gibson H, Carroll N, Clauge JE, Edwards RHT: Exercise performance and fatiguability in patients with chronic fatigue syndrome. J Neurol Neurosurg Psych 56:993–998, 1993Google Scholar
  15. 15.
    Hamilos DL, Nutter D, Gershtenson J, Redmond DP, Clementi JD, Schmaling KB, Make BJ, Jones JF: Core body temperature is normal in chronic fatigue syndrome. Biol Psych 43:293–302, 1998Google Scholar
  16. 16.
    Williams G, Pirmohamed J, Minors D, Waterhouse J, Buchan I, Arendt J, Edwards RH: Dissociation of body temperature and melatonin secretion circadian rhythms in patients with chronic fatigue syndrome. Clin Physiol 16:327–337, 1996Google Scholar
  17. 17.
    Dinarello CA: Biologic basis for interleukin-1 in disease. Blood 87:2095–2147, 1996Google Scholar
  18. 18.
    Cannon JG, Meydani SN, Fielding RA, Fiatarone MA, Meydani M, Farhangmehr M, Orencole SF, Blumberg JB, Evans WJ: The acute phase response in exercise. II. Associations between vitamin E, cytokines and muscle proteolysis. Am J Physiol 260:R1235-R1240, 1991Google Scholar
  19. 19.
    Pacifici R, Brown C, Puscheck E, Friedrich E, Slatopolsky E, Maggio D, McCracken R, Avioli LV: Effect of surgical menopause and estrogen replacement on cytokine release from human blood mononuclear cells. Proc Natl Acad Sci USA 88:5134–5138, 1991Google Scholar
  20. 20.
    Jacob AI, Goldberg PK, Bloom N, Degenshein GA, Kozinn PJ: Endotoxin and bacteria in portal blood. Gastroenterology 72:1268–1270, 1977Google Scholar
  21. 21.
    Cannon JG, Abad LW, Vannier E, Lynch EA: Menstrual-and gender-dependent variations in circulation IL-1 agonists, antagonists and binding proteins. J Leuk Biol 63:117–123, 1998Google Scholar
  22. 22.
    Peterson PK, Sirr SA, Grammith FC, Schenck CH, Pheley AM, Hu S, Chao CC: Effects of mild exercise on cytokines and cerebral blood flow in chronic fatigue syndrome patients. Clin Diagn Lab Immunol 1:222–226, 1994Google Scholar
  23. 23.
    Natelson BH, Ellis SP, Braonain PJO, DeLuca J, Tapp WN: Frequency of deviant immunological test values in chronic fatigue syndrome patients. Clin Diagn Lab Immunol 2:238–240, 1995Google Scholar
  24. 24.
    LaManca JJ, Sisto SA, Zhou X-d, Ottenweller JE, Cook S, Peckerman A, Zhang Q, Denny TN, Gause WC, Natelson BH: Immunological response in chronic fatigue syndrome following a graded exercise test to exhaustion. J Clin Immunol 19:135–142, 1999Google Scholar
  25. 25.
    Arnold DL, Bore PJ, Radda GK, Styles P, Taylor DJ: Excessive intracellular acidosis of skeletal muscle on exercise in a patient with a post-viral exhaustion/fatigue syndrome. Lancet 1:1367–1369, 1984Google Scholar
  26. 26.
    Russell WD: On the current status of rated perceived exertion. Percept Motor Skills 84:799–808, 1997Google Scholar
  27. 27.
    Lloyd AR, Gandevia SC, Hales JP: Muscle performance, voluntary activation, twitch properties and perceived effort in normal subjects and patients with the chronic fatigue syndrome. Brain 114:85–98, 1991Google Scholar
  28. 28.
    Glaser R, and Kiecolt-Glaser JK: Stress-associated immune modulation: Relevance to viral infections and chronic fatigue syndrome. Am J Med 105(3A):35S-42S, 1998Google Scholar
  29. 29.
    Demitrack MA: Neuroendocrine aspects of chronic fatigue syndrome: A commentary. Am J Med 105(3A):11S-14S, 1998Google Scholar
  30. 30.
    Rowe PC, Calkins H: Neurally mediated hypotension and chronic fatigue syndrome. Am J Med 105(3A):15S-21S, 1998Google Scholar

Copyright information

© Plenum Publishing Corporation 1999

Authors and Affiliations

  • Joseph G. Cannon
    • 1
    • 2
  • Jonathan B. Angel
    • 1
  • Richard W. Ball
    • 2
  • Leslie W. Abad
    • 3
  • Laura Fagioli
    • 4
  • Anthony L. Komaroff
    • 4
  1. 1.Department of MedicineNew England Medical CenterBoston
  2. 2.Noll Physiological Research CenterPennsylvania State UniversityUniversity Park
  3. 3.Noll LaboratoryPennsylvania State UniversityUniversity Park
  4. 4.USDA Jean Mayer Human Nutrition Research Center on AgingTufts UniversityBoston

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