Elucidating the unexplained underperformance syndrome in endurance athletes : the interleukin-6 hypothesis

Sports Med. 2003;33(10):771-81. doi: 10.2165/00007256-200333100-00004.


The unexplained underperformance syndrome (UPS), previously known as the overtraining syndrome (OTS), has been defined as a persistent decrement in athletic performance capacity despite 2 weeks of relative rest. It has been proposed that UPS may be caused by excessive cytokine release during and following exercise causing a chronic inflammatory state and 'cytokine sickness'. This article extends that hypothesis by proposing that time-dependent sensitisation could provide a model through which the aetiology of UPS may be explained. In this model, the principal abnormal factors in UPS are an increased production of and/or intolerance to interleukin (IL)-6 during exercise. Strategies to attenuate the IL-6 response to exercise that may also reduce an athlete's susceptibility to UPS are proposed.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Fatigue / blood*
  • Fatigue / etiology
  • Fatigue / genetics
  • Fatigue / psychology
  • Humans
  • Interleukin-6 / blood*
  • Interleukin-6 / genetics
  • Interleukin-6 / physiology
  • Physical Endurance / physiology
  • Sports* / physiology
  • Sports* / psychology
  • Stress, Psychological / blood
  • Stress, Psychological / complications
  • Syndrome


  • Interleukin-6