INCREASED SERUM LEVELS OF INTERLEUKIN-8 IN PATIENTS WITH TENSION-TYPE HEADACHE RENAN B DOMINGUES, HALINA DUARTE, NATA´LIA P ROCHA AND ANTONIO L TEIXEIRA

Oleh: dr. Caisar Riana

ABSTRACT

BACKGROUND AND OBJECTIVES

Patophysiology of Tension Type Headache?????

↑ peripheral level of pro inflammatory cytokines happen in

several chronic pain

How is the

peripheral levels of chemokin

es in patients

with TTH??

METHODS This was a cross sectional study. This study evaluating serum levels of

chemokines in age and sex-matched tension-type headache patients, ictally and interictally, and control participants.

Beck Depression and Anxiety Inventories were recorded.

RESULTS Interleukin-8 levels were significantly

increased in patients with tension-type headache.

Anxiety and depression scores were higher in patients with tension-type headache.

Patients with headache at the time of assessment had increased monocyte chemoattractant protein-1 levels.

CONCLUSION“Pro-inflammatory mechanisms may participate in tension-type headache pathophysiology”

KeywordsTension-type headache, inflammation, chemokines, chronic tension-type headache, episodic tension-type headache, depression, anxiety

INTRODUCTION

TTH = the most frequent form of headache

Little is known about its pathophysiology

Both peripheral & central mechanisms have been implicated

Inflammation may be implicated

Inflammation may play a role in peripheral and central sensitization in patients with TTH

IN PREVIOUS STUDY:• Increased level of IL-6

were found in patients with both episodic & chronic TTH.

• IL-1 beta & IL-18 increased in chronic TTH

• TTH has been associated with psychiatric comorbidities, including depression and anxiety disorders

•Such disorders have been previously associated with increased expression of proinflammatory mediators

Chemokines are a family of small (8–10 kDa) proteins that can induce chemotaxis of inflammatory cells to sites of inflammation and their activation.

According to thenumber and spacing of cysteine residues, four chemokines subfamilies have been identified: CC; CXC; C; CX3C.

CC chemokines, the largest group, are characterized by the presence of two adjacent cysteine residues near the N-terminus

CXC is the second largestgroup and presents a single amino acid between the firsttwo cysteine residues

Aims of this StudyTo compare the serum chemokine levels between TTH patients and

healthy controls

To investigate whether chemokine levels in TTH could be influenced by

psychiatric comorbidities such as depression and anxiety.

METHODS

PATIENTS AND PROCEDURES This cross-sectional study includes patients

with TTH and healthy controls. June to September, 2011, 48 patients with

TTH, enrolled from the headache clinic of the Santa Casa de Miserico´rdia Hospital, Vitoria, Brazil.

The diagnoses were performed in accordance with the International Classification on Headache Disorders – 2n.d edition.

Control subjects were recruited in waiting rooms (with no history of previous primary headache).

INCLUSION AND EXCLUSION Inclusion: minimal age is 18 y.o. Exclusion:

Subjects with inflammatory, infectious, allergic, autoimmune, hepatic, neurodegenerative and neoplasic diseases were not included in the study, as well as pregnant women and people in use of corticosteroids or immunosuppressive drugs.

LEGALLITY This study received full approval by the

Ethics Committee on Research of the ‘Escola Superior de Ciencias da Santa Casa de Vitoria’, Vitoria, Brazil

Informed consent was obtained from each participant.

Demographic (age, body mass index (BMI), race and marital status) and headache features (time of disease, frequency of attacks in the last month) data were recorded.

Anxiety was evaluated with the Beck Anxiety Inventory (BAI) and depression with the Beck Depression Inventory (BDI).

The anxiety symptoms were classified as mild (BAI 8–15), moderate (BAI 16–25) and severe (BAI>25).

The depressive symptoms were classified as minimal (BDI 0–9), mild (BDI 10–18), moderate (BDI 19–29) and severe (BDI 30–63).

CHEMOKINES ASSESSMENT 8 ml whole blood was collected at the same

time (between 09:00 and 11:00). Serum was obtained after centrifugation and

kept at -80oC until ANALYSIS. This measuring determine levels of the

chemokines monocyte chemoattractant protein-1(MCP-1), macrophage inflammatory protein-1a(MIP-1a), regulated on activation, normal T cell expressed and secreted (RANTES), eotaxin, eotaxin-2, interleukin-8 (IL-8), and interferon gamma induced protein 10 (IP-10).

TABLE 1. LIST OF NAMES AND ABBREVIATION OF MEASURED CHEMOKINES

STATISTICAL ANALYSIS The data were analysed with SPSS, version

15.0 for Windows. Verification of normal distribution of data was

performed using the Kolmogorov–Smirnov test.

Mann–Whitney was used for the medians comparisons of continuous data.

Demographic categorical characteristics were compared using chi-square analyses.

Binary logistic regression analysis was performed with the presence of TTH and the type of TTH as the dependent variables.

RESULTS Patients with TTH had

higher median BDI (P¼0.041) and median BAI (P¼0.014) whencompared with controls.

Four (8.3%) TTH patients had moderate to severe and 44 (91.7%) had no or mild anxiety symptoms.

Forty-three TTH patients had minimal to mild (89.6%) and 5 (10.4%) had moderate to severe depression symptoms according to BDI score.

COMPARISON OF INTERLEUKIN-8 (IL-8) LEVELS BETWEEN TENSION-TYPE HEADACHE (TTH) PATIENTS (N=48) AND CONTROLS (N=48)

There were no significant differences in chemokines levels when TTH patients were categorized according to the severity of anxiety and depressive symptoms

FIGURE 2.COMPARISON OF CCL2/MONOCYTE CHEMOATTRACTANT PROTEIN-1 (MCP-1) LEVELS BETWEEN TENSION-TYPE HEADACHE (TTH) PATIENTS WITH (N=14) AND WITHOUT (N=34) HEADACHE PAIN

DISCUSSION

IL-8 is a chemokine produced by macrophages and other cell types exposed to different inflammatory stimuli.

The pro-inflammatory role of this chemokine has been shown in several pathological conditions.

It has been shown that inflammation may enhance nociceptive signalling by affecting peripheral nerve and neuronal excitability.

Elevated eotaxin and MCP-1 levels were found in patients with chronic TTH; however, this difference was not significant after adjusted analysis.

Anxiety and depression symptoms were higher in patients with TTH.

There is growing evidence that anxiety and depression can lead to increased production of pro-inflammatory cytokines.

However, in the present study, TTH patients with moderate and severe anxiety and depression scores had no increase in chemokine levels as compared with patients with mild anxiety and depression scores.

Moreover, anxiety and depression symptoms did not influence the increased levels of IL-8 that showed to be independently associated with TTH.

In conclusion, the present study showed a mild increase of IL-8 serum levels in TTH and an increase of MCP-1 associated with TTH headache pain, suggesting that inflammation has a role in TTH pathophysiology.

Future and larger studies are still needed to assess the role of inflammation in TTH chronification.

CLINICAL IMPLICATION

IL-8 levels were increased in tension-type headache.

MCP-1 levels were higher in patients with headache at the time of assessment.

There were no differences in chemokine levels between episodic and chronic tension type headache.

Pro-inflammatory mechanisms may participate in tension-type headache pathophysiology.

THANK YOU...