Systemic immune response in whiplash injury and ankle sprain: elevated IL-6 and IL-10. Clin Immunol 2001 Oct;101(1):106-12

Size: px

Start display at page:

Download "Systemic immune response in whiplash injury and ankle sprain: elevated IL-6 and IL-10. Clin Immunol 2001 Oct;101(1):106-12"

Wilfrid Richardson
6 years ago
Views:

1 1 Systemic immune response in whiplash injury and ankle sprain: elevated IL-6 and IL-10. Clin Immunol 2001 Oct;101(1): Kivioja J, Ozenci V, Rinaldi L, Kouwenhoven M, Lindgren U, Link H. FROM ABSTRACT: Whiplash injury and whiplash-associated disorders (WAD) are significant problems of modern society. Numerous attempts have been made to characterize the nature of whiplash injury. Whether the immune system is involved during the disease process is not known. In a prospective study, using enzyme-linked immunospot (ELISPOT) assays, we examined numbers of blood mononuclear cells (MNC) secreting pro- (IFNgamma, TNF-alpha, IL-6) and anti-inflammatory (IL-10) cytokines in patients with WAD and, for reference, patients with ankle sprain and multiple sclerosis and healthy subjects. An immune response reflected by elevated numbers of TNF-alpha- and IL-10- secreting blood MNC was observed in patients with WAD examined within 3 days compared to 14 days after the whiplash injury. The patients with WAD examined within 3 days after the injury had also higher numbers of IL-6 and IL-10 secreting blood MNC compared to healthy subjects. The alterations of cytokine profiles observed in WAD were also observed in patients with ankle sprain when examined within 3 days after trauma. In contrast, there were no differences for cytokine profiles between patients with WAD examined 14 days after the whiplash injury and healthy subjects. Relatively minor trauma like WAD and ankle sprain are associated with a systemic dysregulation in numbers of cells secreting pro- as well as antiinflammatory cytokines.

2 2 THESE AUTHORS ALSO NOTE: In whiplash patients, unless there are distinct neurological signs, it is difficult to assess the nature and seriousness of injury by physical examination and magnetic resonance imaging studies. Until now, there are no methods of demonstrating any injured tissue in patients with WAD. To understand the pathogenesis of WAD, it is important to identify measurable alteration(s) taking place during the disease process. Ankle sprain is an injury that can be easily diagnosed by clinical examination, and nearly all patients recover completely. In whiplash injury, there is often no visible signs of injury. The immune system is a powerful, complex entity composed of numerous cell types and regulatory mechanisms. It is known that immune responses are induced by many factors, including trauma. Many changes within the immune system, triggered by trauma, might ultimately be deleterious and lead to complications such as systemic inflammatory response syndrome (SIRS) and even multiple system organ failure. Cytokines are the main orchestrators of immune responses, determining the type of immune response that will take place and perpetuate after induction. Cytokines can be divided into two major subgroups: (1) T helper (Th) 1 type cytokines (IFN-gamma, IL-2, TNF-alpha) induce cellular immune responses. (2) Th2 cytokines (IL-4, IL-5, IL-6, IL-10) mainly augment humoral immunity. The role of cytokines in major trauma and shock has been widely studied. The involvement of cytokines in minor trauma like WAD and ankle sprain is not known. This study focuses on systemic immune responses in whiplash and 3 control groups:

3 3 (1) Patients with ankle sprain (2) Healthy subjects (3) Patients with multiple sclerosis (MS) MS is an inflammatoy demyelinating disease of the central nervous system associated with dysregulation of the cytokines. MATERIAL AND METHODS 27 whiplash patients with a mean age of 35 years. Inclusion criteria were car accident within the last 3 days, age between 18 and 65 years. Exclusion criteria were previous neck injury, abnormal signs on neurological examination, and cervical fracture or dislocation. None of the patients received nonsteroid anti-inflammatory drugs during the study period. [This is important because these drugs alter the immune system response]. According to the Quebec classification, 23 patients had WAD grade II and 4 patients had WAD grade III. Control group (1) consisted of 14 patients with acute ankle sprain, mean age of 35 years. Their ankles showed visible hematoma. They were examined within 3 days after the ankle sprain. Control group (2) consisted of 23 healthy subjects with a mean age of 32 years. Control group (3) consisted of 27 MS patients with a mean age of 43 years. From all, blood was obtained by venous puncture, mononuclear cells (MNCs) were separated, and analyzed. RESULTS WHIPLASH GROUP Within 3 days: Increased levels of Th2 cytokines. In those 4 patients who were Quebec classification WAD grade III, they had increased levels of both Th1 and Th2 cytokines. [IMPORTANT]. WHIPLASH GROUP at 14 days: Same levels of Th2 cytokines as healthy group.

4 4 ANKLE SPRAIN GROUP Increased levels of Th2 cytokines. HEALTHY GROUP Normal levels of Th1 and Th2 cytokines. MS GROUP Lower levels of Th2 cytokines compared to healthy group. DISCUSSION Analysis of cytokine profiles is becoming increasingly important for understanding physiological responses and pathological mechanisms associated with immune stimulation and improving therapies. Despite the growing awareness that cytokines play an important role in a wide variety of clinical disorders, measurements of cytokines are hampered by their complex biology. ELISPOT assays [for detection of cytokine secreting cells] are among the most sensitive and specific assays available for cytokine research. They permit the ex vivo identification of cells actively secreting cytokines without any prior stimulation in vitro. ELISPOT assays are times more sensitive than other methods and are more efficient, and faster. Using ELISPOT assays, we found that acute WAD is associated with detectable immune responses systematically. Numbers of both Th1 and Th2 cytokines in blood MNC were higher in patients with acute whiplash and ankle sprain as compared to healthy subjects. The findings suggest that in acute whiplash and ankle sprain that both Th1 and Th2 responses are activated in parallel. This study also suggests that trauma activation of the immune system that could be of importance for the development of signs and symptoms associated with WAD and ankle sprain. Elevated levels of cytokine-secreting cells systemically might reflect accumulation of immune cells in the traumatized tissue in WAD as well as in ankle sprain.

5 5 We consider it to be of great interest that acute minor trauma is associated with elevated production of certain cytokines, detectable systemically. This observation could constitute a basis for future studies of other immune mediators in these and related (e.g., long-lasting symptoms after WAD) clinical events. CONCLUSIONS (1) Patients with acute whiplash injury display a systemic increase of Th1 and Th2 cytokines. (2) Patients with acute ankle sprain show a similar cytokine profile as acute whiplash patients, indicating that measurements of cytokines under study do not discriminate between acute WAD and ankle sprain. (3) The immune system response noted by cytokine-secreting cells is different in acute minor trauma compared to MS. KEY POINTS FROM DAN MURPHY: (1) One can not assess the nature and seriousness of whiplash injury by physical examination and magnetic resonance imaging studies. (2) An immune system response is induced by trauma, and this can be assessed only in the acute stage by using enzyme-linked immunospot (ELISPOT) assays of immune system cytokine profile. (3) Quebec classification WAD grade III patients (those with neurological signs) had an increased immune system response as compared to WAD grade II patients (increased levels of both Th1 and Th2 cytokines). (4) Acute trauma activation of the immune system could document whiplash trauma. (5) The elevated levels of cytokine-secreting cells systemically following trauma might reflect an accumulation of immune cells in the traumatized tissue. (6) The only clinical methods to demonstrate injured tissues in whiplash patients is the enzyme-linked immunospot (ELISPOT) assay cytokine profile, as indicated in this article.

Dynamic kine magnetic resonance imaging in whiplash patients. Pain Research and Management 2009 Nov-Dec 2009;Vol. 14, No. 6; pp.

Dynamic kine magnetic resonance imaging in whiplash patients 1 Pain Research and Management 2009 Nov-Dec 2009;Vol. 14, No. 6; pp. 427-32 Lindgren KA, Kettunen JA, Paatelma M, Mikkonen RH. FROM ABSTRACT: