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Biomedical subjects

M J Jacobs

Publications and source records attributed to M J Jacobs.

At least 73 records · Page 4Linked to original sources
PubMed1996

The spinal component to skin blood flow abnormalities in reflex sympathetic dystrophy.

OBJECTIVE: To determine whether the mechanisms of reflex sympathetic dystrophy, a neuropathic pain syndrome characterized by skin blood flow abnormalities associated with sympathetic vasoconstrictor and antidromic vasodilator mechanisms, are solely of peripheral origin or have an additional spinal component and act exclusively through neural or also involve humoral pathways. PATIENTS: The 54 patients with unilateral reflex sympathetic dystrophy were divided into the following three stages according to their perception of skin temperature in the clinically affected hand: stage I, stationary warmth sensation; stage II, intermittent warmth and cold sensation; and stage III, stationary cold sensation. METHODS: Investigation of basal skin blood flow and vasoconstrictive response to dependency of skin microvessels in the clinically unaffected hand and the clinically affected hand of patients with reflex sympathetic dystrophy and the left hand of 16 control subjects. Microcirculation was investigated at the predominantly neurally controlled thermoregulatory level (Doppler laser flowmetry) and at the predominantly humorally controlled nutritive level (capillary microscopy). RESULTS: In the clinically unaffected hand, at the thermoregulatory level of the microcirculation: (1) basal skin blood flow was increased at stage I compared with the control subjects, whereas no differences could be observed at this stage compared with the clinically affected hand; (2) the vasoconstrictive response to dependency (defined as skin blood flow at heart level divided by skin blood flow in the dependent position) was attenuated at stage I compared with the control subjects, whereas no differences could be observed at this stage compared with the clinically affected hand; and (3) basal skin blood flow and the vasoconstrictive response to dependency did not differ from the control subjects at stages II and III. In the clinically unaffected hand, at the nutritive level, no differences could be observed at any stage of the syndrome compared with the control subjects. CONCLUSIONS: This study indicates that there is a spinal component to microcirculatory abnormalities at stage I of the reflex sympathetic dystrophy syndrome that most likely acts through neural (antidromic vasodilator) mechanisms and that may be initiated by traumatic excitation of a peripheral nerve on the clinically affected side.

Adult↗
PubMed1996

Diagnosis of arterial disease of the lower extremities with duplex ultrasonography.

The development of duplex scanning carries the prospect of an entire non-invasive work-up of patients with peripheral arterial occlusive disease. To obtain the best available estimates of its diagnostic accuracy, a meta-analysis of 71 studies evaluating duplex scanning was performed. Independent methodological judgement left 16 studies for data extraction. Pooled estimates (95 per cent confidence interval of sensitivity and specificity for detection of a stenosis greater than or equal to 50 per cent or occlusion in the aortoiliac tract were 86 (80-91) per cent and 97 (95-99) per cent respectively. The results for the femoropopliteal tract compared well with this, with a sensitivity of 80 (74-85) per cent and a specificity of 96 (94-98) per cent. The accuracy of detection of a stenosis greater than or equal to 50 per cent or an occlusion in the infragenicular arteries was lower with a sensitivity and specificity of 83 (59-96) per cent and 84 (69-93) per cent respectively. Duplex scanning is an accurate tool for assessment of atherosclerotic lesions in the aortoiliac and femoropopliteal tract and can replace routine preinterventional angiography in a substantial number of patients.

Aorta↗
PubMed1996

Skin blood flow disturbances in the contralateral limb in a peripheral mononeuropathy in the rat.

Electrical excitation of nociceptive afferents in an extremity has been demonstrated to increase skin blood flow in the contralateral extremity. Hence, one would expect that loose sciatic nerve ligation, which induces an experimental painful peripheral neuropathy, may also provoke a vasodilator response in the contralateral hindpaw. On the non-ligated side, such a response may involve inhibited skin vasoconstrictor activity as well as neurogenically mediated active vasodilation. We studied skin blood flow changes in the rat hindpaw consequent to contralateral loose sciatic nerve ligation. After ligation, we also investigated whether blockade of afferent input from the ligated sciatic nerve to the spinal cord, by means of lidocaine, overrules the vasodilator response in the non-ligated paw. On the non-ligated side, we assessed the vasoconstrictor response of skin microvessels to cooling of the rat abdomen as a measure of skin vasoconstrictor activity in this paw. In order to investigate the involvement of sensory and/or non-sensory nerve fibers in the non-ligated sciatic nerve on skin blood flow abnormalities in the non-ligated paw, we studied the influence of blockade of these fibers through successive capsaicin and lidocaine application. We show that loose ligation of the sciatic nerve induces a vasodilator response in the contralateral hindpaw, which is completely abolished by blockade of afferent input from the ligated sciatic nerve. From day 1 after ligation, skin vasoconstrictor activity in the non-ligated paw was reduced, as indicated by an impaired vasoconstrictor response to cooling of the rat abdomen. Besides, blockade of sensory but not of non-sensory nerve fibers on the non-ligated side attenuated the vasodilator response in this paw. The data presented here indicate that loose ligation of the rat sciatic nerve induces a vasodilator response in the contralateral hindpaw. On the non-ligated side, this vasodilator response may involve inhibition of skin vasoconstrictor activity, as well as antidromically acting sensory nerve fibers.

Animals↗
PubMed1996

Reflex sympathetic dystrophy: does sympathetic dysfunction originate from peripheral neuropathy?

BACKGROUND: Sympathetic dysfunction in reflex sympathetic dystrophy (RSD) has been purported to consist of an afferently-induced increase in efferent sympathetic nerve impulses (somato-sympathetic reflex) and/or denervation-induced supersensitivity to catecholamines. In addition, both the central and peripheral nervous systems have been claimed to be involved. It was the aim of this study to obtain more insights into these underlying mechanisms. METHODS: In the affected extremeties of 42 patients with RSD we investigated as indirect measures of sympathetic (dys)function: (1) skin blood flow and the vasoconstrictive response to dependency of skin microvessels by means of laser Doppler flowmetry (distal to the site of trauma), (2) relative distention of the brachial artery and changes in relative distention consequent to a cold pressor test by means of ultrasonic vessel wall tracking (proximal to the site of trauma), and (3) arterial blood pressures by means of the Finapres technique. Both provocation tests induce a sympathetically mediated response. Patients were divided into three categories according to their perception of skin temperature in their injured limb (stage I, stationary warmth sensation; stage II, intermittent warmth and cold sensation; or stage III, stationary cold sensation). RESULTS: Distal to the site of trauma, when compared with controls, skin blood flow was increased at stage I and decreased at stages II and III, whereas the vasoconstrictive response to dependency was impaired at all three stages. Proximally, when compared with controls, relative distention of the brachial artery and its response to the cold pressor test were decreased at all three stages. No differences were observed in pulse pressure between patient groups and controls. CONCLUSIONS: These results suggest that sympathetic dysfunction in extremities of patients with RSD distal to the site of trauma consists of hypersensitivity to catecholamines at stages II and III as a result of autonomic denervation at stage I, whereas proximal to the site of trauma sympathetic nerve impulses may be increased at all three stages.

Adult↗
PubMed1996

Function of cryopreserved arterial allografts under immunosuppressive protection with cyclosporine A.

PURPOSE: Cryopreserved arterial allografts may be used for arterial reconstructive procedures. In this experimental study cryopreserved arteries were used as autografts and as allografts with or without immunosuppression with cyclosporine A. METHODS: In group A (three dogs, six bilateral grafts) cryopreserved carotid artery autografts were implanted. In groups B and C female mongrel dogs (three dogs and six bilateral grafts in each group) received cryopreserved male carotid artery allografts. Dogs in group C were treated with cyclosporine A (25 mg/kg/day). After 3 months of implantation patency was assessed by angiography. Contractile responses to KCl and phenylephrine (Phe) and the endothelium-dependent relaxation response to methacholine (Met) were examined in segments of the grafts after excision. Medial thickness was assessed semiquantitatively. The grafts were stained for sex chromatin analysis to determine the origin of cells in allografts. RESULTS: Patency: group A, 100% (6 of 6), group B, 66.6% (4 of 6), and group C, 100% (6 of 6). Functional responses: before implantation, after thawing, 2.7 +/- 0.5 mN (KCl), 4.8 +/- 1.0 mN (Phe), and 0.0% +/- 0.0% (Met), group A, 36.9 +/- 10.6 mN (KCl), 31.5 +/- 14.4 mN (Phe), and 59.3% +/- 20.4% (Met), group B, 0 for all agents used, group C, 34.0 +/- 7.5 mN (KCl), 28.8 +/- 7.0 mN (Phe), and 46.2% +/- 3.2% (Met). Morphologic characteristics: the media of grafts in group B showed significant thinning (p < 0.05). Smooth-muscle cells in vessel walls of grafts in group C were of female origin. CONCLUSION: Arteries showed no function and loss of endothelial integrity after cryopreservation and thawing. After 3 months of implantation cryopreserved arterial autografts and allografts under immunosuppressive treatment with cyclosporine A showed 100% patency and return of functional responses resulting from repopulation of grafts by host cells.

Animals↗
PubMed1996

Increasing incidence of aneurysms of the abdominal aorta in The Netherlands.

OBJECTIVES: To study the trend in incidence of aneurysms of the abdominal aorta in The Netherlands during the past two decades. SETTING: The Dutch population from 1972 to 1992. DESIGN: Analysis of all hospital admissions and deaths due to aneurysms of the abdominal aorta. OUTCOME MEASURES: Age adjusted and age specific mortality and discharge rates. In-hospital mortality after surgery upon aneurysms of the abdominal aorta. RESULTS: From 1972 to 1992 age adjusted mortality from aneurysms of the abdominal aorta rose from 3.1 to 8.1 per 100,000 in men, and from 1.4 to 2.2 in women. Age adjusted discharge rates (alive and dead) for non-ruptured abdominal aortic aneurysms increased from 3.7 to 37.6 per 100,000 in men and from 1.2 to 5.5 in women. For ruptured aneurysms, the age adjusted discharge rates increased from 2.4 to 10.3 per 100,000 in men and from 0.7 to 1.7 in women. Age adjusted in-hospital mortality after surgery upon non-ruptured aneurysms was halved from 13% in 1972 to 7% in 1992, mortality after acute repair upon ruptured aneurysms also decreased from 52% in 1972 to 36% in 1992. CONCLUSIONS: There was an impressive increase in the hospital based incidence for aneurysms of the abdominal aorta during the past two decades in The Netherlands. An improved detection rate through ultrasound is probably a major contributor to this increase, but gender differences and the rise in the number of ruptured aneurysms suggest that a real increase in incidence may exist, especially in men. Surgical outcome for both ruptured and non-ruptured aneurysms of the abdominal aorta improved.

Age Distribution↗
PubMed1996

A comparison of the sensitivity of epidural and myogenic transcranial motor-evoked responses in the detection of acute spinal cord ischemia in the rabbit.

Monitoring motor-evoked responses to transcranial stimulation (tc-MERs) provides information about the functional status of the spinal cord during operations that pose the risk of spinal cord ischemia. Responses can be recorded from the epidural space (epidural tc-MERs) or from muscle (myogenic tc-MERs). In this study the relative sensitivity of epidural and myogenic tc-MERs to acute spinal cord ischemia was compared. Spinal cord ischemia was produced by infrarenal aortic balloon occlusion in nine anesthetized New Zealand White rabbits. Tc-MERs were evoked by transcranial electrical stimuli applied to the scalp. Responses were recorded from the lumbar epidural space and from the soleus muscle, and the effect of aortic occlusion was assessed. The peak-to-peak amplitude of the direct wave of the epidural response decreased gradually during aortic occlusion in eight animals and increased in one. The median (10th to 90th percentiles) time to a 50% reduction in amplitude was 11.3 (3-22) min. In contrast, myogenic responses disappeared within 2 min after the start of occlusion in all animals. Lower extremity ischemia as a cause of changes in myogenic tc-MER amplitude was excluded by ligating the right femoral artery and demonstrating that myogenic responses were preserved for 30 min, before occluding the aorta. We conclude that myogenic responses are more sensitive to acute spinal cord ischemia than epidural responses. The rapid detection of spinal cord ischemia with transcranial myogenic motor-evoked responses could be of clinical use in assessing the adequacy of spinal cord blood flow during operations where the spinal cord is at risk.

Acute Disease↗
PubMed1996

Influence of partial nerve injury in the rat on efferent function of sympathetic and antidromically acting sensory nerve fibers.

OBJECTIVE: To investigate how partial injury of a large peripheral nerve affects efferent (vasomotor) function of sympathetic and antidromically acting sensory nerve fibers. DESIGN: Randomized animal study. MATERIALS AND METHODS: We assessed, by laser Doppler flowmetry, skin blood flow (SBF) in the hindpaw of male Lewis rats before partial injury of the ipsilateral sciatic nerve (through loose ligation) as well as at an early stage (day 4) and at a later stage (day 21) after this procedure. This procedure has been reported to induce signs and symptoms like those observed in patients with causalgia. At the two time points after nerve injury, SBF was assessed before and after (chemical) blockade of sensory and nonsensory (sympathetic) sciatic nerve fibers. Furthermore, at day 21 we measured the density of sympathetic nerve fibers in footpad arteries. MEASUREMENTS AND MAIN RESULTS: At day 4, compared with preligation values, we observed an increase in SBF that was reduced by blockade of sensory nerve fibers. Subsequent blockade of nonsensory nerve fibers further reduced SBF. At day 21, SBF was decreased compared with preligation values. Blockade of sensory nerve fibers further reduced SBF, and subsequent blockade of nonsensory nerve fibers did so as well. The density of sympathetic nerve fibers was lower on the ligated side than on the nonligated side. CONCLUSIONS: Partial injury of the rat sciatic nerve causes an ipsilateral increase in SBF at an early stage, which is followed by a decrease at a later stage. At both stages, antidromically acting sensory and orthodromically acting nonsensory (sympathetic) nerve fibers are involved in the vasodilator response. At a later stage, however, neurogenic vasodilator mechanisms are overruled by a nonneurogenic vasoconstrictor mechanism. The latter may consist of supersensitivity of skin microvessels to catecholamines consequent to reduced neurogenic disposition of catecholamines.

Animals↗
PubMed1996

Arterial thrombosis below the inguinal ligament: percutaneous treatment with a thrombosuction catheter.

PURPOSE: To assess the safety and clinical efficacy of using a thrombosuction catheter for treatment of arterial thrombosis below the inguinal ligament. MATERIALS AND METHODS: The catheter was used in a consecutive group of 28 patients (10 women, 18 men; age range, 38-87 years; mean age, 66.7 years; with 11 native vessels and 17 grafts) with acute infrainguinal thrombosis. Initial local success, clinical success, and 30-day outcome were studied. RESULTS: The initial local success rate was 82%. The clinical success rate was 73% for native vessels and 53% for grafts. The 30-day success rate was 73% for native vessels and 35% for grafts. Displacement of thrombotic material during the procedure resulted in a clinical complication in one patient. There were no bleeding complications. In 58% of all patients (n = 26), no lytic drug was used. CONCLUSION: The thrombosuction catheter seems to be a safe, fast-acting alternative or supplement to local lysis therapy for infrainguinal arterial thrombosis.

Adult↗
PubMed1996

[Forefoot gangrene and infra-crural bypass: simultaneous amputation].

Patients presented for amputation mostly have chronic limb ischaemia caused by atherosclerosis, with signs of severe arterial insufficiency including rest pain, non-healing skin lesions, ulceration or gangrene. Foot infections, especially in diabetic patients, are often multimicrobial, deeply invasive and frequently require aggressive measures, like debridement and drainage or partial open forefoot amputation in addition to broad-spectrum antibiotics, in patients with critical limb ischaemia and limited necrosis and forefoot gangrene, distal bypass surgery is the treatment of choice. The main question is whether amputation should be performed simultaneously or in a secondary stage. Our own experience deals with 342 femorocrural and femoropedal bypass grafts for the treatment of critical limb ischaemia. The results showed no significant difference in graft patency between crural and pedal grafts. Clinical factors like diabetes mellitus, poor distal run-off and site of the distal anastomosis had no adverse effect on the functioning and patency of the graft. In this series we found that in diabetic patients significantly more amputations were required because of persistent foot infection. Since in these patients amputation was performed in a secondary stage, we changed our policy to simultaneous amputation. After completion of the bypass, closure and coverage of all the wounds, the gangrenous part is amputated. In case of deep, wet or infectious gangrene of the forefoot, an open transmetatarsal amputation is performed. Using this approach we have further increased limb-salvage and especially the number of usuable limbs.

Amputation, Surgical↗
PubMed1995

Can transcutaneous oximetry detect nutritive perfusion disturbances in patients with lower limb ischemia?

Transcutaneous oximetry (TcpO2) performed at 37 and 44 degrees on the dorsum of the foot and capillary microscopy of the nailfold of the big toe were applied to 85 patients with various (including asymptomatic) stages of lower limb ischemia to appreciate the relationship between (disturbances in) capillary perfusion and skin oxygen tension. In mildly diseased patients, capillary perfusion as measured by direct observation, was preserved. In critically ischemic patients in the supine position, red blood cell-perfused capillary density was reduced. Nutritive perfusion was severely reduced and showed an absent reactive hyperemia after a 1-min arterial occlusion. Also, postural vasoconstrictive activity was reduced. TcpO2 measured at 37 degrees was very low already in mildly diseased patients, illustrating the poor oxygen diffusion toward the skin. At 44 degrees, TcpO2 was severely reduced in critically ischemic patients. Reactive hyperemic response and postural vasoconstriction were suppressed, due to local heating of the skin. Measurement of the TcpO2 has limitations in the assessment of nutritive perfusion, as opposed to capillary microscopy, since it is an indirect measure of skin perfusion, not necessarily derived from capillaries only. The obligatory local skin heating impairs physiological studies as to hyperemic reserve capacity or postural constriction mechanisms. Thus, transcutaneous oximetry is a poor method of characterizing pathophysiological mechanisms occurring in skin nutritive microcirculation. However, capillary microscopy and transcutaneous oximetry can give additive information as to the severity of peripheral ischemia. Peak red blood cell velocity during reactive hyperemia using capillary microscopy and the resting TcpO2 at 44 degrees, both measured in the supine position, appeared to be valuable microcirculatory parameters in detecting critical limb ischemia.

Adult↗
PubMed1995

Reflex sympathetic dystrophy: evolution of microcirculatory disturbances in time.

Reflex sympathetic dystrophy (RSD) is a pain syndrome that is characterised by autonomic, motor and sensory disturbances. The syndrome has often been associated with sympathetic dysfunction. Therefore, we investigated whether there are disturbances in the sympathetic function of skin microcirculation in the various clinical stages of RSD. Laser Doppler flowmetry (LDF) was used to obtain information about total (mainly thermoregulatory) skin blood flow (TSBF), since blood flow in arteriovenous anastomoses and subpapillary plexus, which are richly innervated by sympathetic nerve endings, contributes predominantly to the flow signal as obtained by LDF. Capillary microscopy was used to appraise whether the trophic changes, as observed in RSD, result from an impaired nutritive skin blood flow (NSBF). Transcutaneous oximetry (TCPO2) was employed as a measure of the oxygenation of superficial skin layers. Skin temperature (ST) was also determined. Patients were divided into 3 clinical stages: stage I in case of a chronic warmth sensation, stage II in case of an intermittent warmth and cold sensation, and stage III in case of a chronic cold sensation. As compared to controls: (1) TSBF was increased (P < 0.05) at stage I and decreased at stages II (P < 0.05) and III (P < 0.001), (2) NSBF was decreased at stages II (P < 0.05) and III (P < 0.001), (3) TCPO2 was not impaired at any stage, (4) ST was increased (P < 0.01) at stage I and decreased (P < 0.05) at stage III. The present study is the first to report an increase of TSBF at stage I of RSD, which may be caused by a decrease in efferent sympathetic nerve impulses. At stages II and III both TSBF and NSBF were decreased which may reflect increased sensitivity of skin microvessels to (circulating) catecholamines.

Adolescent↗
PubMed1995

Morphology and function of dog arterial grafts preserved in UW-solution.

OBJECTIVES: To assess the function of arterial grafts after prolonged preservation in the University of Wisconsin solution (UW), in vitro and in vivo. METHODS: Carotid arteries were harvested from dogs and stored for 1-21 days at 4 degrees C in UW (n = 10) or in PBS (0.9% NaCl, pH 7.4), (PBS) (n = 10). Slices were examined by lightmicroscopy (LM) and scanning electron microscopy (SEM). For viability testing, specimens were connected to an isometric force transducer (2 x n = 9). Contractile and relaxation responses were examined by adding phenylephrine (200 microM) and metacholine (200 microM), respectively. For in vivo studies (n = 41), 2.5cm carotid artery segments were implanted or orthotopically, as autografts and allografts, after 14 days of storage in UW or in PBS. Autologous veins were used as controls. After 28 days or 56 days, arteriography was performed and the grafts were excised for LM and SEM. RESULTS: The arterial endothelial layer remained intact after up to 14 days of storage in UW. In PBS, the endothelium was lost after 3 days. The functional response after 14 days storage in UW was approximately 50% vs. 0% after 14 days in PBS. In the autografts, total patencies (28 days + 56 days) were 100% (8/8) and 63% (5/8) for UW and PBS stored grafts, respectively. In the allografts, the UW and PBS preserved grafts showed total patencies of 86% (12/14) and 83% (5/6), respectively. Microscopically, the allografts showed fibrotic degeneration. CONCLUSIONS: Arteries are well preserved in UW up to 14 days of storage. Arterial autografts preserved in UW showed good patency and better integrity of the vessel wall after implantation, than grafts stored in PBS or allografts (without immunosuppressive therapy).

Adenosine↗
PubMed1995

The influence of local skin heating and reactive hyperaemia on skin blood flow abnormalities in patients with reflex sympathetic dystrophy (RSD).

Skin blood flow in reflex sympathetic dystrophy (RSD) patients has been reported to develop from an increase at an early stage to a decrease at later stages. So far, it remains unclear whether these abnormalities are solely of microcirculatory origin, and result from functional vasospasm or structural vessel wall changes. Eighty-seven RSD patients were categorized as follows: stage I in case of a stationary warmth sensation; stage II in case of an intermittent warmth and cold sensation; and stage III in case of a stationary cold sensation. Laser Doppler flowmetry (LDF) was used as a measure of total skin blood flow and transcutaneous oximetry (TCPO2) as a measure of vascular reactivity in the more superficial skin layers. Local skin heating and reactive hyperaemia were used to study the relative reserve capacity of skin microvessels. Finapres was used to assess digital arterial pressures. As compared to healthy volunteers (n = 16), LDF under control conditions demonstrated an increase in skin blood flow at stage I (P < 0.01). A decrease in skin blood flow under control conditions was seen at stages II (P < 0.05) and III (P < 0.05), but the relative flow reserve capacity, as measured with LDF, was not impaired at these stages. Regression analysis did not show a relation between LDF parameters and duration of the syndrome. TCPO2 revealed no differences between patient groups and controls. Regression analysis did not demonstrate a relation between TCPO2 parameters and duration of the syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Capillary microscopy is a diagnostic aid in patients with acral ischemia.

The diagnosis of peripheral ischemic diseases is a challenge to the vascular specialist, since discrimination of the different entities on clinical grounds is not always clear. Capillary microscopy is a noninvasive diagnostic technique that can visualize in particular the morphology and perfusion of the digital capillaries. The authors investigated all 522 patients who were referred to the vascular laboratory over a six-year period, in an attempt to obtain more certainty about the diagnosis of their acral ischemic complaints. Patients with clinically manifest Raynaud's phenomenon and control subjects were compared to obtain differentiation criteria. Thus, capillary microscopy scored a sensitivity of 67%, a specificity of 84%, and an accuracy of 81% to detect Raynaud's phenomenon. A disturbed capillary morphology was virtually pathognomonic in Raynaud's disease secondary to systemic disorders (specificity 100%); the accuracy was but 74%. In 69% of the patients with clinically atypical acral ischemia, capillary microscopy yielded a diagnosis. Digital blood pressure measurements, however, appeared of no use in the diagnosis of Raynaud's phenomenon. Hence, capillary microscopy appears to be a useful aid in the diagnosis of acral ischemic syndromes.

Adolescent↗
PubMed1995

Role of interleukin 1 in antigen-induced exacerbations of murine arthritis.

The mechanism underlying the chronic and intermittent course of rheumatoid arthritis is not elucidated. In the present study, the role of interleukin 1 (IL-1) was investigated in exacerbations of antigen-induced arthritis in mice. A flare-up of smoldering inflammation (weeks 3 to 4 of antigen-induced arthritis) was inducible by injection of a small amount of methylated bovine serum albumin into the hypersensitive knee joint. Immunohistochemistry showed IL-1 expression in the synovial lining layer and in focal areas of the inflamed synovium during the flare-up. IL-1 was also measured in 1-hour culture supernatant of synovial tissue taken during the flare-up by a bioassay. The expression of both immunoreactive and bioactive IL-1 in the hypersensitive joint peaked around 6 hours after antigen (2 micrograms of methylated bovine serum albumin) injection and declined thereafter. Antigen rechallenge induced an acute joint swelling of the arthritic joint but not in the naive joint of the sensitized mouse, yet synovia of both joints produced IL-1 after antigen injection. Remarkably, a single intravenous injection of rabbit anti-IL-1 alpha and -beta antibodies 1 hour before antigen rechallenge neutralized IL-1 in the joint. Anti-IL-1 treatment significantly reduced the antigen-induced joint swelling (30 to 40%) but did not affect the profound influx of polymorphonuclear cells in the onset of the exacerbation. However, a profound relief of the inflammation (synovitis) was obtained by IL-1 blockade on day 4 of the exacerbation. Chondrocyte proteoglycan synthesis was markedly suppressed in the antigen-challenged naive knee joints suggesting that this was a direct IL-1 effect as the inflammation was insignificant. Anti-IL-1 treatment was able to maintain chondrocyte proteoglycan synthesis in the antigen-rechallenged joint, which was highly suppressed in the control group. Furthermore, the enhanced proteoglycan breakdown in the antigen-rechallenged joints was significantly decreased in the anti-IL-1 group. We concluded that IL-1 is an important mediator in exacerbations of murine arthritis, and amelioration of cartilage pathology was obtained with anti-IL-1 antibody treatment.

Animals↗