Periodontal Health in Children with Juvenile idiopathic arthritis.

AIM: To investigate gingival inflammation and prevalence of four specific periodontal associated pathogens in Juvenile idiopathic arthritis (JIA) in relation to orofacial pain, jaw function and systemic inflammatory activity in JIA. METHODS: Forty-five children with JIA and 16 healthy children as controls, were enrolled. Subjects were examined and classified according to the diagnostic criteria for temporomandibular disorders (DC/TMD). Pain, pain-related disability and jaw function were also assessed. A clinical periodontal examination was performed. Subgingival plaque samples were collected and analyzed for semiquantitative levels of the following periodontal pathogens; Aggregatibacter actinomycetemcomintans, Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola. CONCLUSION: This study suggests that the periodontal disease-associated bacteria P. gingivalis and T. forsythia do not contribute to neither periodontal disease, systemic inflammatory activity nor orofacial pain and jaw dysfunction, including TMJ arthritis, in JIA patients in Sweden.

Juvenile idiopathic arthritis and the temporomandibular joint: a case-control study of magnetic resonance imaging findings in relation to clinical and psychosocial factors.

AIM: In juvenile idiopathic arthritis (JIA), the temporomandibular joint (TMJ) is a particularly challenging joint to assess both clinically and with imaging. The aim of this article is to investigate TMJ magnetic resonance imaging (MRI) findings in relation to clinical and psychosocial factors in patients with JIA and healthy individuals related to TMJ arthritis in JIA. MATERIALS: In total, 45 patients (6-16 years) with JIA and 16 healthy age- and sex-matched controls were examined according to the diagnostic criteria for temporomandibular disorders (DC/TMD). The subjects answered questionnaires about psychosocial factors (pain intensity, pain-related disability, depression, stress, catastrophising, pain locations, and jaw function) and underwent bilateral MRI of the TMJ. CONCLUSION: This study indicates a substantial overlap of TMJ MRI findings in both the inflammatory domain and the damage domain between JIA patients and healthy individuals. In JIA patients, the inflammatory MRI sign of bone marrow oedema seems to influence orofacial pain intensity.

Diagnostic criteria for temporomandibular disorders: Diagnostic accuracy for general dentistry procedure without mandatory commands regarding myalgia, arthralgia and headache attributed to temporomandibular disorder.

The clinical examination in diagnostic criteria for temporomandibular disorders (DC/TMD) is a strict procedure and comprises mandatory commands. However, learning and using these mandatory commands in general practice have proven to be difficult and their use of DC/TMD is minimal. To investigate whether reliability on a diagnostic level for DC/TMD diagnoses differs between examiners using the mandatory commands or not. Six examiners were divided into two groups: one using the mandatory commands in DC/TMD for the clinical examination and one who did not use the mandatory commands. A reliability assessment was performed twice, one occasion for each group of examiners. The assessment was performed according to the guidelines from the International Network for Orofacial Pain and Related Disorders Methodology. Each group of examiners thereby examined 16 subjects (11 TMD patients and 5 healthy individuals) each, and the diagnostic agreement (reliability) as compared to diagnoses derived by a reference standard examiner was calculated with Cohen' s kappa coefficient. The DC/TMD diagnoses myalgia, arthralgia and headache attributed to TMD were included in the reliability assessment. There was no significant difference regarding diagnostic agreement reliability between the examiners using or not using the mandatory DC/TMD commands. This study indicates that not using the mandatory commands in DC/TMD in general practice does not impair the diagnostic reliability regarding the diagnoses myalgia, arthralgia and headache attributed to TMD compared to including the commands.

Clinical diagnosis of temporomandibular joint arthritis.

Evidence-based clinical diagnostic criteria for temporomandibular joint (TMJ) arthritis are not available. To establish (i) criteria for clinical diagnosis of TMJ arthritis and (ii) clinical variables useful to determine inflammatory activity in TMJ arthritis using synovial fluid levels of inflammatory mediators as the reference standard. A calibrated examiner assessed TMJ pain, function, noise and occlusal changes in 219 TMJs (141 patients, 15 healthy individuals). TMJ synovial fluid samples were obtained with a push-pull technique using the hydroxycobalamin method and analysed for TNF, TNFsRII, IL-1ß, IL-1ra, IL-1sRII, IL-6 and serotonin. If any inflammatory mediator concentration exceeded normal, the TMJ was considered as arthritic. In the patient group, 71% of the joints were arthritic. Of those, 93% were painful. About 66% of the non-arthritic TMJs were painful to some degree. Intensity of TMJ resting pain and TMJ maximum opening pain, number of jaw movements causing TMJ pain and laterotrusive movement to the contralateral side significantly explained presence of arthritis (AUC 0.72, P < .001). Based on these findings, criteria for possible, probable and definite TMJ arthritis were determined. Arthritic TMJs with high inflammatory activity showed higher pain intensity on maximum mouth opening (P < .001) and higher number of painful mandibular movements (P = .004) than TMJs with low inflammatory activity. The combination TMJ pain on maximum mouth opening and Contralateral laterotrusion <8 mm appears to have diagnostic value for TMJ arthritis. Among arthritic TMJs, higher TMJ pain intensity on maximum mouth opening and number of mandibular movements causing TMJ pain indicates higher inflammatory activity.

Assessment of a training programme on detection of temporomandibular joint osseous changes applying pre-defined 2D multiplane cone beam computed tomography reconstructions.

OBJECTIVES: Osseous changes in temporomandibular joint disorders (TMD) are common indications for cone beam computed tomography (CBCT). The number of such cases is increasing while a number of qualified oral radiologists is limited. This study investigated the usefulness of a training programme for general dental practitioners (GDPs) regarding temporomandibular joint (TMJ) osseous changes detection in CBCT images. METHODS: We selected CBCT images of 35 TMD cases and chose 5 of them to use in training 7 GDPs on detecting osseous changes in the TMJ. In evaluation directly following training, GDPs assessed the 30 remaining cases. Three qualified radiologists served as reference standard. A 2-month follow-up of training comprising evaluation of the same cases. The cases are assessed according to Ahmad et al (Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 107, 2009, 844) protocol of TMJ osseous changes in CBCT images. RESULTS: Sensitivity and specificity of the CBCT protocol were high, except for some criteria that did not appear in the cases. Average observer sensitivity was 65% while specificity was 87%. Average correct individual response rate was 84%. Mean agreement among the GDPs was 73%. Observer performance had improved at the 2-month follow-up. CONCLUSION: The present educational programme could be a helpful material on recognising possible osseous changes of TMJ and it can be used as a part of a training programme for GDP and for specialist candidates.

Pharmacological treatment of oro-facial pain - health technology assessment including a systematic review with network meta-analysis.

This health technology assessment evaluated the efficacy of pharmacological treatment in patients with oro-facial pain. Randomised controlled trials were included if they reported pharmacological treatment in patients ≥18 years with chronic (≥3 months) oro-facial pain. Patients were divided into subgroups: TMD-muscle [temporomandibular disorders (TMD) mainly associated with myalgia]; TMD-joint (TMD mainly associated with temporomandibular joint pain); and burning mouth syndrome (BMS). The primary outcome was pain intensity reduction after pharmacological treatment. The scientific quality of the evidence was rated according to GRADE. An electronic search in PubMed, Cochrane Library, and EMBASE from database inception to 1 March 2017 combined with a handsearch identified 1552 articles. After screening of abstracts, 178 articles were reviewed in full text and 57 studies met the inclusion criteria. After risk of bias assessment, 41 articles remained: 15 studies on 790 patients classified as TMD-joint, nine on 375 patients classified as TMD-muscle and 17 on 868 patients with BMS. Of these, eight studies on TMD-muscle, and five on BMS were included in separate network meta-analysis. The narrative synthesis suggests that NSAIDs as well as corticosteroid and hyaluronate injections are effective treatments for TMD-joint pain. The network meta-analysis showed that clonazepam and capsaicin reduced pain intensity in BMS, and the muscle relaxant cyclobenzaprine, for the TMD-muscle group. In conclusion, based on a limited number of studies, evidence provided with network meta-analysis showed that clonazepam and capsaicin are effective in treatment of BMS and that the muscle relaxant cyclobenzaprine has a positive treatment effect for TMD-muscle pain.

Diagnostic criteria for temporomandibular disorders (DC/TMD): interexaminer reliability of the Finnish version of Axis I clinical diagnoses.

Recently, updated diagnostic criteria for temporomandibular disorders (DC/TMD) were published to assess TMD in a standardised way in clinical and research settings. The DC/TMD protocol has been translated into Finnish using specific cultural equivalency procedures. To assess the interexaminer reliability using the Finnish translations of the DC/TMD-FIN Axis I clinical diagnostic assessment instruments. Reliability assessment data were collected during a 1-day DC/TMD Examiner Training Course at the University of Turku, Finland, in collaboration with the International DC/TMD Training and Calibration Center in Malmö University. Clinical TMD examinations according to the Finnish pre-final version of the DC/TMD Axis I assessment protocol were performed by four experienced TMD specialists on altogether 16 models. Kappa coefficient, overall percentage agreement (%A) as well as positive (PA) and negative (NA) agreements were used to define the reliability. Myofascial pain with referral, headache attributed to TMD and disc displacement (DD) without reduction without limited opening showed excellent kappa values (range 0·87-1·00). Fair-to-good reliability was observed for diagnoses of myalgia (k = 0·67), arthralgia (k = 0·71) and DD with reduction (k = 0·64). The PA was high for all pain-related diagnoses and DD without reduction without limited opening (medians ≥83%), and acceptable for DD with reduction (median 67%). The NA was high (medians ≥87%) for all DC/TMD diagnoses, except for myalgia which showed acceptable NA (median 75%). The %A was high for all assessed diagnoses (medians >85%). The findings of this study showed DC/TMD-FIN Axis I to demonstrate sufficiently high reliability for pain-related TMD diagnoses.

Professional knowledge among Swedish and Saudi healthcare practitioners regarding oro-facial pain in children and adolescents.

Oro-facial pain (OFP) and temporomandibular disorders (TMD) in children and adolescents are a growing problem. To meet patients' healthcare needs, professionals must perform their work intuitively and with quality. Therefore, a high degree of professional knowledge is necessary. To investigate the professional knowledge regarding OFP/TMD in children and adolescents among Swedish and Saudi Arabian dental and medical specialists compared with Swedish OFP specialists. One questionnaire including the four domains Chronic pain and behaviour; Aetiology; Diagnosis and classification; Treatment and prognosis was distributed to 383 potential participants, that is physicians and dentists in Sweden and Saudi Arabia. The Swedish OFP/TMD specialists were used as a reference group. The response rates from Sweden and Saudi Arabia were 49% and 86%, respectively. The degree of agreement was highest in the domain Chronic pain and behaviour, especially for the Swedish groups. Regarding the other three domains, the agreement was modest to poor. In general, Swedish groups showed a higher agreement with Swedish OFP/TMD specialists than Saudi Arabian groups. This study shows that professional knowledge regarding OFP/TMD in children and adolescents is limited among Swedish and Saudi Arabian dental and medical professionals compared to Swedish OFP/TMD specialists. In Swedish groups, the professional knowledge is more accurate than in the corresponding Saudi Arabian. With these results in mind, and the frequent prevalence of OFP/TMD in children and adolescents, one can draw the conclusion that there is a need for modern medical education regarding OFP/TMD among both physicians and dentists, especially in Saudi Arabia.

Cytokines in healthy temporomandibular joint synovial fluid.

Analysis of temporomandibular joint (TMJ) synovial fluid may elucidate the aetiology of temporomandibular disorders and arthritic conditions, as well as the inflammatory mechanisms involved. Knowledge about healthy synovial fluid is necessary to understand TMJ pathologies. We aimed to quantify the proinflammatory cytokines interleukin (IL)-1ß, IL-2, IL-6 and tumour necrosis factor (TNF), and the anti-inflammatory cytokines IL-10 and interferon (IFN)-γ in healthy TMJ synovial fluid to serve as reference values for future studies on TMJ pathologies. Twenty healthy, young adult volunteers without temporomandibular dysfunction were included. Bilateral synovial fluid samples were obtained using the push-pull technique with hydroxocobalamin described by Alstergren in 1999. Cytokines were quantified with Luminex multiplex assays and compared using nonparametric statistical analysis. No serious adverse effects were reported. Of 40 possible samples, 14 fulfilled the strict sampling criteria and were included in the analysis. Cytokine values (reported as medians with interquartile ranges) were as follows: TNF, 23 (13-37) pg mL(-1) ; IL-2, 1·8 (0-22) pg mL(-1) ; and INF-γ, 10 (0-47) pg mL(-1) . IL-1ß, IL-6 and IL-10 were almost undetectable. In addition, TNF and INF-γ cytokine levels correlated. We demonstrated that TNF was consistently detected and IFN-γ and IL-2 sporadically detected in the TMJ synovial fluid of healthy individuals using the hydroxocobalamin method and a multiplex assay. The cytokines IL-10, IL-1ß and IL-6 were barely detectable in this sample of healthy TMJs.

Expanding the taxonomy of the diagnostic criteria for temporomandibular disorders.

There is a need to expand the current temporomandibular disorders' (TMDs) classification to include less common but clinically important disorders. The immediate aim was to develop a consensus-based classification system and associated diagnostic criteria that have clinical and research utility for less common TMDs. The long-term aim was to establish a foundation, vis-à-vis this classification system, that will stimulate data collection, validity testing and further criteria refinement. A working group [members of the International RDC/TMD Consortium Network of the International Association for Dental Research (IADR), members of the Orofacial Pain Special Interest Group (SIG) of the International Association for the Study of Pain (IASP), and members from other professional societies] reviewed disorders for inclusion based on clinical significance, the availability of plausible diagnostic criteria and the ability to operationalise and study the criteria. The disorders were derived from the literature when possible and based on expert opinion as necessary. The expanded TMDs taxonomy was presented for feedback at international meetings. Of 56 disorders considered, 37 were included in the expanded taxonomy and were placed into the following four categories: temporomandibular joint disorders, masticatory muscle disorders, headache disorders and disorders affecting associated structures. Those excluded were extremely uncommon, lacking operationalised diagnostic criteria, not clearly related to TMDs, or not sufficiently distinct from disorders already included within the taxonomy. The expanded TMDs taxonomy offers an integrated approach to clinical diagnosis and provides a framework for further research to operationalise and test the proposed taxonomy and diagnostic criteria.

Successful treatment with multiple intra-articular injections of infliximab in a patient with psoriatic arthritis.

This case report presents the clinical and radiographic course of temporomandibular joint (TMJ) involvement in a patient with severe TMJ symptoms from psoriatic arthritis (PsA) resistant to both systemic infliximab and intra-articular glucocorticoid and who therefore received multiple intra-articular infliximab injections for 36 weeks. TMJ symptoms improved after the first bilateral intra-articular infliximab injections but even more so after the second injections. The considerable improvement remained for the 36 weeks studied. Bilateral computerized tomography showed no progression in radiographic changes during the treatment. No adverse reaction was observed from the intra-articular injections.

Interleukin-1beta influences the effect of infliximab on temporomandibular joint pain in rheumatoid arthritis.

OBJECTIVES: The aim of this study was to investigate the influence of plasma and synovial fluid tumour necrosis factor alpha (TNFalpha), interleukin-1beta (IL-1beta), IL-6, soluble TNF receptor II (TNF-sRII), IL-1 receptor antagonist (IL-1ra), soluble IL-1 receptor II (IL-1sRII) and IL-10 on the effect of the TNFalpha antibody infliximab on temporomandibular joint (TMJ) pain in patients with active rheumatoid arthritis (RA). METHODS: Fifteen patients with TMJ pain taking methotrexate were included in the study. The effect of intravenous infusions of infliximab was assessed after 14 or 22 weeks. TMJ resting and movement pain was assessed by a visual analogue scale (VAS) (0-100 mm) and samples of venous blood and TMJ synovial fluid were collected before and after treatment. RESULTS: The effect of infliximab on TMJ pain was influenced by pretreatment plasma levels of IL-1beta, IL-1ra, and IL-10 as well as pretreatment levels of TMJ synovial fluid IL-1sRII. High pretreatment levels of these cytokines and receptors as well as the presence of rheumatoid factor (RF) were associated with no or minor reduction in TMJ pain after treatment. CONCLUSIONS: Systemic treatment of RA with a combination of infliximab and methotrexate seems to be insufficient to alleviate TMJ pain in patients with RF or high pretreatment plasma levels of IL-1beta.

Radiographic signs of bone destruction in the arthritic temporomandibular joint with special reference to markers of disease activity. A longitudinal study.

OBJECTIVE: To investigate the progression of radiographic changes of the temporomandibular joint (TMJ) with reference to plasma levels of interleukin-1beta (IL-1beta), C-reactive protein (CRP) and disease duration. METHODS: Twenty-one patients with chronic inflammatory joint disease and TMJ involvement were included. Individualized tomography of the TMJ was performed twice with an interval of at least 12 months. Blood samples were analysed for IL-1beta and CRP. RESULTS: Significant progression of the overall grade of radiographic changes occurred during the observation period, whereas erosions showed great interindividual variability. Progression of TMJ bone loss was correlated to raised levels of CRP and, in patients with a diagnosis of rheumatoid arthritis, or with shorter duration, also to plasma IL-1beta. CONCLUSION: Progression of overall grade of radiographic changes in the TMJ occurs in patients with chronic inflammatory joint disease. Raised levels of serum CRP are associated with progression of TMJ bone loss.

Interleukin-1beta in antigen-induced arthritis of the rabbit temporomandibular joint.

The aim was to investigate joint perfusate levels of interleukin-1beta (IL-1beta) in antigen-induced monoarthritis of the rabbit temporomandibular (TMJ) and knee joints. Twenty-four adult male New Zealand White rabbits were divided into three groups: a control group as well as TMJ arthritis and knee joint arthritis groups. After sensitization, unilateral arthritis was induced by intra-articular injection with ovalbumin and the contralateral joint was injected with saline 3 weeks after induction of arthritis. Joints were then perfused continuously with saline and samples were collected at 10-min intervals over a 50-min period. The IL-1beta concentrations in the samples were then analyzed. After killing the animals, the joints were examined histologically. The IL-1beta concentrations in the samples from the arthritic TMJs and knee joints were significantly higher than in the saline-injected and the control joints. Histological signs of chronic arthritis of similar severity were found in both joints. The IL-1beta levels in the samples from the arthritic TM and knee joints correlated with the histological severity of the arthritis, including pannus formation. In conclusion, this study shows that IL-1beta is released in the synovium of rabbit TMJs and knee joints during antigen-induced arthritis, and that high IL-1beta levels in synovial fluid are associated with histological signs of inflammation including, pannus tissue formation.

Pain mediation by prostaglandin E2 and leukotriene B4 in the human masseter muscle.

The pathophysiology behind chronic pain from masticatory muscles is unclear. Our hypothesis was that this pain is of inflammatory origin and associated with release of inflammatory mediators. The aim of this study was therefore to investigate the presence of prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) in the masseter muscle and plasma and their relation to myalgia. Nineteen patients with fibromyalgia, 19 with local myalgia of the masseter muscle, and 11 healthy individuals were examined with regard to local muscular pain intensity at rest and pressure pain threshold. Inclusion criteria were masseter muscle pain for at least 3 months and masseter muscle tenderness on digital palpation. Samples were obtained from the masseter muscle by microdialysis, and the dialysates and venous blood samples were analyzed with regard to PGE2 and LTB4 concentration. Intramuscular levels were found in all groups, with significantly higher levels of LTB4 in the patients with fibromyalgia, in whom PGE2 was positively correlated to muscular pain. In the healthy individuals PGE2 was negatively correlated to pressure pain threshold. In both patient groups but not in the healthy individuals LTB4 increased during the consecutive samplings. PGE2 and LTB4 were detectable in the plasma of all groups. In conclusion, both PGE2 and LTB4 were found in the human masseter muscle. LTB4 levels are increased on needle trauma in patients with myalgia. PGE2 levels are related to muscular pain in patients with fibromyalgia. Masseter muscle pain therefore seems to be partly of peripheral inflammatory origin in fibromyalgia.

Tumor necrosis factor-alpha in synovial fluid and plasma from patients with chronic connective tissue disease and its relation to temporomandibular joint pain.

PURPOSE: The purpose of this study was to determine the level of tumor necrosis factor-alpha (TNF-alpha) in the temporomandibular joint (TMJ) synovial fluid (SF-TNF-alpha) and blood plasma (P-TNF-alpha) of patients with chronic inflammatory connective tissue disease and investigate its relation to TMJ pain, hyperalgesia, and allodynia. PATIENTS AND METHODS: Twenty-four patients with a diagnosis of chronic inflammatory connective tissue disease and TMJ pain were included in the study. Visual analog scale, tenderness of the TMJ, and pain at mandibular movements were registered, and the pressure pain threshold and pressure pain tolerance levels were measured. TMJ synovial fluid samples and blood plasma were analyzed for TNF-alpha and the levels related to TMJ pain, hyperalgesia, and allodynia. RESULTS: TNF-alpha was present in the TMJ synovial fluid of 8 of 24 patients at levels significantly exceeding those in plasma at the same visit. The presence of SF-TNF-alpha showed a significant positive correlation to TMJ pain at maximum voluntary mouth opening and tenderness to posterior palpation of the TMJ. CONCLUSION: Local production of TNF-alpha occurs in the TMJ synovium of patients with chronic inflammatory connective tissue disease. Pain on mandibular movement and tenderness on posterior palpation (allodynia) of the TMJ is related to the level of SF-TNF-alpha.

Prostaglandin E2 in temporomandibular joint synovial fluid and its relation to pain and inflammatory disorders.

PURPOSE: The aim of this study was to investigate temporomandibular joint (TMJ) synovial fluid (SF) levels of prostaglandin E2 and its relation to general inflammatory activity and its influence on specific TMJ pain in patients with inflammatory TMJ disorders. PATIENTS AND METHODS: The study comprised 24 patients (30 joints) with inflammatory TMJ disorders and 4 healthy persons (6 joints). TMJ pain at rest, tenderness to palpation of the TMJ, and TMJ pressure pain threshold, as well as pain during joint movements (PM), were assessed. PGE2 levels were analyzed in synovial fluid samples (SF-PGE2) and blood plasma (P-PGE2). The erythrocyte sedimentation rate (B-ESR) as well as the serum levels of C-reactive protein (S-CRP) and antinuclear antibodies were determined. RESULTS: PGE2 was undetectable in the plasma and in the TMJ SF of the healthy persons. In the patients, PGE2 was detectable in 20 of the 30 (67%) SF samples. SF-PGE2 was significantly and positively correlated to PM in the patients. There were significant correlations between P-PGE2 and B-ESR as well as the S-CRP. CONCLUSIONS: This study shows that the synovial fluid in patients with TMJ inflammatory disorders frequently has a detectable level of PGE2 that is related to TMJ allodynia. The plasma levels of PGE2 seem to be related to the general inflammatory activity in these patients.

Immediate effects of the serotonin antagonist granisetron on temporomandibular joint pain in patients with systemic inflammatory disorders.

The aim of this study was to investigate if the 5-HT3 antagonist granisetron reduces temporomandibular joint (TMJ) pain in patients with systemic inflammatory joint disorders. Sixteen patients with systemic inflammatory joint disease with pain localized over the TMJ region and tenderness to digital palpation of the TMJ were included. The current resting pain (VASRest) and the pain during maximum mouth opening (VAS(MVM)) of the TMJs were assessed with a 100 mm visual analogue scale. An electronic pressure algometer was used to estimate the pressure pain threshold (PPT) over the lateral aspect of the TMJ. Venous blood was collected for measurement of the plasma and serum levels of 5-HT, erythrocyte sedimentation rate, rheumatoid factor and C-reactive protein. The selective 5-HT3 receptor antagonist granisetron or saline were injected into the posterior part of the upper TMJ compartment in a randomized double-blind manner. The patients in the granisetron group had lower VASRest than the patients in the saline group after 10 min. In the granisetron group, VASRest was decreased after 10 min, while VAS(MVM) was decreased and PPT increased after 20 min. In the saline group, VAS(MVM) was decreased after 20 min. In conclusion, granisetron has an immediate, short-lasting and specific pain reducing effect in TMJ inflammatory arthritis. The 5-HT3 receptor may therefore be involved in the mediation of TMJ pain in systemic inflammatory joint disorders.

Cytokines in temporomandibular joint arthritis.

As the article in the current issue by Shinoda and colleagues shows, during the last two decades, there has been a dramatic increase in the understanding of basic biology behind chronic temporomandibular joint (TMJ) pain, inflammation and destruction. The involvement and contribution of cytokines to TMJ pain and inflammation must now be considered as established, evident and fundamental. Based on the present knowledge, it is now possible to design and investigate novel therapeutic strategies. These new and very encouraging approaches include manipulation of cytokine function, immune reactivity and the behaviour of inflammatory cells while maintaining the integrity of the affected tissue.