Topical ibuprofen decreases thromboxane release from the endotoxin-stimulated burn wound

A full-thickness burn wound in adult sheep releases prostanoids when they are injected locally with E. coli endotoxin, 2 micrograms/kg, resulting in an increase in pulmonary artery pressure (Ppa) from 20 +/- 3 to 34 +/- 5 mm Hg, and a decrease in mean arterial oxygen tension (PaO2) from 88 +/- 6 to 70 +/- 5 torr; this corresponds to an increase in venous plasma TxB2 content from a baseline of 220 +/- 79 pg/ml to 440 +/- 90 pg/ml. Burn prostanoid production, measured in lymph, increased ten- to fifteen-fold for both thromboxane A2, measured as TxB2, and prostacyclin, 6-keto-PGF1 alpha. The intravenous administration of ibuprofen, 12.5 mg/kg, eliminated both the increase in Ppa and decrease in PaO2 as well as the increase in burn lymph prostanoids. However, plasma prostanoids were also decreased below baseline, a potentially deleterious effect. A topical ibuprofen cream, 5% ibuprofen in a water-soluble ester, was applied to the burn hide every 6 hrs x 4 after which endotoxin was again injected below the hide. The pulmonary dysfunction was prevented as was the increase in plasma TxB2 with the value remaining at baseline. Burn lymph levels were only increased three- to five fold. Ibuprofen levels in burn lymph were maintained at 1-2 mcg/ml. The addition of the cream to the burn, however, did increase the wound bacterial content to 10(5)-10(7) bacteria/gram of tissue compared to 10(2)-10(3) for the dry, untreated burn, probably due to softening of the burn. Topically applied ibuprofen, therefore, can decrease burn wound prostanoid production from local endotoxin, preventing lung dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)     

An unusually large, solid tumor of the parotid gland

Burn injury is known to cause thrombosis and occlusion of dermal vessels that come in direct contact with thermal energy. Progressive ischemia secondary to diminished blood flow may compromise dermal tissues immediately surrounding the primary burn site. A standardized brass bar was used to create uniform full-thickness "comb" burns on 10 rat backs. Topical petrolatum (N = 2), 2% nitroglycerin (N = 4), and 5% flurbiprofen (N = 4) was applied to the burns at 2 and 4 hours postinjury. The vascular patency of dermal vessels was visualized directly by latex vascular casts made 24 hours after the burn injury. The vascular casts showed an absence of patent vessels within the direct burn sites in all treatment groups, and within the burn interspaces of the petrolatum-treated rats. Interspacial dermal vessel patency was seen in the 2% nitroglycerin and 5% flurbiprofen-treated rats. Topical 2% nitroglycerin and 5% flurbiprofen applied 2 and 4 hours postinjury effectively prevented interspacial dermal vessel thrombosis at 24 hours postinjury.     

Comparison of the postburn hyperdynamic state and changes in lung function (effect of wound bacterial content)

The pulmonary and systemic response to a full-thickness burn (15% of total body surface area) was determined in 15 adult sheep. Also compared was the effect of wound bacterial content and prostanoid release on this response. Burn wound thromboxane A2, measured as TxB2, and prostacyclin, measured as 6-keto-PGF1 alpha, were measured in burn wound lymph. Animals were monitored for 7 days. On the final day, a full-thickness biopsy specimen of burn tissue was obtained for quantitative bacteriology. Wounds with 10(4) or less organisms per gram of burn tissue were considered colonized, whereas those with 10(5) or more organisms per gram of burn tissue indicated wound infection. Seven sheep had 10(4) or less bacteria and the remaining eight sheep had 10(6) or greater bacteria. We noted a significant mean increase in cardiac index from a baseline of 5 to 6.2 L/min/m2, a decrease in systemic vascular resistance from 16 to 12 mm Hg/L/min, and a mean increase in oxygen consumption from a baseline of 135 to 165 ml/min/m2 during the 7-day study period. There were no differences in these responses between the colonized and the infected wounds. Pulmonary artery pressure increased from a mean baseline of 19 to 24 mm Hg and arterial oxygen tension (PaO2) decreased from a baseline of 90 to 80 mm Hg in the infected wound group, with values remaining at baseline in the colonized wound group. These changes corresponded with an increase in lymph and plasma TxB2 from a baseline of 200 to 210 pg/ml to 1000 +/- 250 and 600 +/- 190 pg/ml, respectively. Values in the animals with colonized wounds were not significantly increased.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ibuprofen in acute-care therapy.

Ibuprofen is a potent cyclooxygenase inhibitor known to reduce the production of arachidonic acid metabolites. Prostacyclin and thromboxane are well-studied metabolites that play a prominent role in inflammation. Many of the effects of ibuprofen can be linked to its anti-inflammatory properties. Beneficial results from ibuprofen therapy have been documented, and more widespread use of the drug seems indicated. Conditions ranging from immunologic response to trauma and sepsis to postburn lung dysfunction to wound edema are improved by the use of ibuprofen. The fact that ibuprofen is effective in the various conditions detailed above, while other steroidal and nonsteroidal drugs are effective only in selective instances, increases the value of ibuprofen. Other properties of the drug, aside from its anti-inflammatory effects, are not as well studied and not as well known. Their importance, however, should not be overlooked. Superoxide radical tissue injury may be very important in acute injury and this phenomenon needs further study. In several studies ibuprofen has been shown to antagonize this type of injury. Similarly fibrinolysis inhibition is known to occur in burn wounds, but its role in other injuries is unknown. The antagonism of this inhibitor by ibuprofen maintains vascular patency. The clinical use of ibuprofen will increase as research further elucidates the mechanisms of tissue injury in acute situations and the many and varied mechanisms of action of ibuprofen.     

Elucidating the vascular response to burns with a new rat model.

Burn injury causes acute thrombosis and occlusion of vessels in the dermis directly killed by thermal energy. A vascular response also occurs in the uninjured dermis bordering the site of injury. Diminished blood flow leads to progressive ischemia and necrosis in the dermis beneath and surrounding the burn. If blood flow is maintained or restored in this area, the tissue survives. A noninvasive technique for studying dynamic changes in blood flow in this transitional dermis in rats is presented. A rectangular brass bar 19 mm wide with 5-mm transverse notches was heated in boiling water and applied to the skin surface for 20 seconds, making a "comb" burn composed of a row of four rectangular 10 x 19-mm full-thickness burns. Between the burns were 5 x 19-mm bands of uninjured skin, called "interspaces." After burning, blood flow near the surface of both the burn sites and the interspaces was monitored with a laser Doppler perfusion monitor for 24 hours. The vascular patency of blood vessels was directly visualized by latex vascular casts made 24 hours after burn. The possible prevention of progressive ischemia by injecting systemic ibuprofen was examined in this new model. Normal skin has a surface blood flow reading of 80 +/- 16 mV, burn sites have a reading of 11 +/- 4 mV, and interspaces have a reading of 21 +/- 4 mV at 24 hours postburn in untreated rats. Systemic ibuprofen given IM immediately postburn at 12.5 mg/kg increased blood flow to 80 +/- 28 mV within the interspaces, to 17 +/- 12 mV in the burn site, and to 80 +/- 9 mV in normal skin. The vascular casts showed an absence of patent vessels within both the burn sites and interspaces in untreated rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

Postburn immunosuppression in an animal model. II. Restoration of cell-mediated immunity by immunomodulating drugs

We used a model of full-thickness burn injury in the mouse and quantitated cell-mediated immunity (CMI) by measuring the degree of sensitization to the contact antigen, 2,4-dinitrofluorobenzene (DNFB). Our previous studies have shown that CMI in the burned mouse is severely suppressed. Using this immunosuppression model, we were able to significantly restore CMI by treating animals following the burn injury either with one of the nonsteroidal anti-inflammatory drugs ibuprofen or indomethacin or with the cytotoxic alkylating agent cyclophosphamide. These drugs probably restore CMI by inhibiting generation of suppressor T lymphocytes in the burned host.     

Specific aspects of the treatment of patients with multiple mechanical and burn injuries

Fewer than 5 percent of all burn patients sustain other traumatic injuries before, during, or immediately after their accident. Multiple traumas associated with a burn injury create special problems during the care of the thermally injured patients. Conversely, the burn injury often complicates the diagnosis and treatment of the trauma. The combination of mechanical and burn injuries can be divided into two types: a) any associated fracture located outside the burned area, or b) fractured bones within the burned area. This situation represents a critical factor which must be taken into account during treatment procedures. The following options should be considered: in fractures outside the burned area, there would be no difference in standard, skeletal treatment procedures. For the treatment of fractures in burned areas (mostly on the extremities), the optimal procedure is osteosynthesis within 48 hours of the burn trauma, when the burn wound is nearly sterile (without significant bacterial colonisation). We prefer two-team surgery. Firstly, a trauma surgeon performs osteosynthesis and, after that, burn surgeons treat the burns. The optimal approach in full-thickness burns would be necrectomy and autografting. This is, however, not always possible, because of the overall condition of the patient who has been continuously resuscitated during the shock period. All individual factors must be considered during the decision-making process.     

Alterations of angiotensin II receptor levels in full-thickness excisional wounds in rat skin

Angiotensin II was recently shown to have a growth-promoting role after vascular injury and in the development of cardiac hypertrophy and fibrosis. In addition, angiotensin II may play a role in dermal wound repair. In this article, alterations in angiotensin II receptor levels in tissue harvested from full-thickness excisional dermal wounds in adult Sprague-Dawley rats were examined. A 2.25 cm(2) full-thickness excision of the dorsal skin was made under general anesthesia, and the tissue was harvested on days 1, 3, 5, 7, and 10 after wounding. The level of (125)I-Sar(1).IIe(8)-angiotensin II bound to membrane preparations of both granulation tissue and wound edge increased from day 1, peaked on day 5, and returned to nonsurgical levels by day 10. In both granulation and wound edge segments of the injured skin, the maximum binding on postoperative day 5 was about twice that of postoperative day 1 tissue or control skin. Competitive binding studies with angiotensin II type 1 receptor or type 2 receptor antagonists (DuP 753 and CGP 42112B, respectively) showed that the receptors present in the healing dermal tissue from the adult rat were almost entirely of the type 1 receptor form.     

The effect of indomethacin on burn-induced immunosuppression

Recent interest in the role of prostaglandin inhibitors as immunomodulators following major injury prompted us to study the effect of indomethacin on burn-induced immunosuppression in rats as measured by the delayed-type hypersensitivity (DTH) skin test response, ability to contain an intradermal bacterial challenge (10(8) Staphylococcus aureus 502A injected intradermally), and overall survival from spontaneous burn wound sepsis. Fifty male Sprague-Dawley rats sensitized to keyhole limpet hemocyanin (KLH) were subjected to a 30% full-thickness scald burn. Group 1 (n = 24) received indomethacin at 0.5 mg/kg intraperitoneally once daily with the first dose given immediately following the burn. Group 2 (n = 24) received vehicle only. Prostaglandin E2 measured by radioimmunoassay on day 17 was 2553 +/- 832 pcg/ml serum (+/- SEM) in the vehicle group and 1042 +/- 231 pcg/ml in the indomethacin group (P = 0.058, unpaired t test). Burn injury induced a decrease in the DTH response to KLH and an increase in the Staph lesion size (P less than 0.05) which was not corrected by indomethacin treatment. All animals developed spontaneous burn wound sepsis by day 14. Survival after 17 days in the indomethacin group was 100% compared to that of the vehicle group, 79%, P less than 0.05 (Fisher exact test). We conclude that despite unmeasurable corrections of the burn-induced suppression of the DTH response and local nonspecific bacterial defenses, low-dose indomethacin improves survival following burn sepsis.     

Effect of PGI2 and thromboxane antagonist on liver ischemic injury

Thromboxane, prostacyclin and their ratio could play an important role in the ischemic liver injury. To study this hypothesis, thromboxane and prostacyclin were measured by RIA after incubation of liver tissues removed during and after an ischemia of 90 min in male Wistar rats. The thromboxane to prostacyclin ratio increases during this period. In order to examine if this change could influence the survival rate of animals submitted to the same period of ischemia, drugs able to reduce the relative predominance of thromboxane were infused. The survival rate was not modified by administration of Iloprost or Daltroban, the antagonist of the thromboxane receptors. By contrast, imidazole, an inhibitor of thromboxane synthetase, significantly increased the survival rate. The same result was obtained with the administration of Daltroban plus Iloprost, suggesting that the reduction of thromboxane action associated with the increase of PGI2 level reduces the ischemic injury.     

Elevated monocyte chemoattractant protein-1 levels following thermal injury precede monocyte recruitment to the wound site and are controlled, in part, by tumor necrosis factor-α

In previous studies, mice given a full-thickness scald injury had an influx of neutrophils into the skin that followed a local increase in a neutrophil chemoattractant. Because macrophages are known to infiltrate the wound area after neutrophils and are essential for normal wound repair, studies were designed to characterize the time course of macrophage accumulation in the wound and to identify the factor(s) responsible for this influx. A macrophage infiltrate into the wound was observed at 4 days post-injury and persisted through at least 10 days. This influx was preceded by an initial fourfold increase in dermal monocyte chemoattractant protein-1 levels at 24 hours post-injury (p < 0.05). This elevation in monocyte chemoattractant protein-1 was enhanced at 4 and 10 days postburn resulting in a sixfold increase over baseline (p < 0.01). Levels of tumor necrosis factor-alpha, a proinflammatory cytokine known to induce chemokine production, were elevated at 90 minutes after injury in burn- versus sham-injured groups (p < 0.05). Furthermore, administration of tumor necrosis factor-alpha neutralizing antibody in vivo reduced the dermal levels of monocyte chemoattractant protein-1 seen at 10 days postburn by 57% (p < 0.01); however, macrophage accumulation was not altered. Thus, elevated systemic TNF-alpha levels may influence the local chemokine milieu following burn injury.     

Modulation of inflammatory and catabolic responses in severely burned children by early burn wound excision in the first 24 hours

HYPOTHESIS: Early burn wound excision modulates the hypermetabolic response in severe pediatric burn injuries. DESIGN: Before-after trial. SETTING: A 30-bed burn referral center in a private, university-affiliated hospital. METHODS: We studied 35 severely burned children who were divided into 2 groups. One group (n = 20) was treated with early burn wound excision within 24 hours after the injury. The second group (n = 15) was treated conservatively with silver sulfadiazine in other burn facilities for 5 days, and burn wounds were surgically excised when patients were admitted to our burn center on day 6 after the injury. Data compiled included oxygen consumption and acute-phase protein, interleukin 1beta; interleukin 6, interleukin 10, tumor necrosis factor alpha, and anabolic hormone (growth hormone, insulinlike growth factor type 1) levels preoperatively and 24 hours and 5 days postoperatively. MAIN OUTCOME MEASURES: Acute-phase and hypermetabolic responses. RESULTS: Early burn wound excision abrogated the hypermetabolic response in pediatric burn patients. Patients who underwent conservative treatment had a significantly more severe inflammatory and hypermetabolic response at the same time interval and significantly lower levels of anabolic hormones. CONCLUSIONS: Early burn wound excision is a safe therapeutic approach that modulates the hypermetabolic response after burn injury. It was superior to the conservative treatment of silver sulfadiazine and delayed excision, and it should be considered when treating all severe full-thickness burns.     

Burn wound assessment in porcine skin using indocyanine green fluorescence.

BACKGROUND: An accurate assessment of deep dermal burns within the first week after burn is still an unresolved clinical problem. Infrared-excited fluorescence of indocyanine green was examined as a method of early determination of burn depth. METHODS: Burns of varying depths were placed on the paraspinal region, flank, and abdomen of swine using a heated brass block. Fluorescence images of the burns were recorded 1, 24, 48, and 72 hours later. RESULTS: The ratio of fluorescence in 64 burn wounds relative to adjacent normal tissue identified wounds that healed and did not heal within 21 days with an accuracy of 100%, after accounting for the age of the burn. Higher fluorescence ratios were observed in newly placed burns relative to older burns having comparable depths. CONCLUSION: Deep partial-thickness burns were differentiated from deep dermal full-thickness burns in a porcine skin burn model independent of body location. Diagnosis was possible between 1 and 72 hours after injury.     

Cardiac release of prostacyclin and thromboxane A2 during coronary revascularization

Cardiac surgery stimulates the systemic synthesis of prostacyclin and thromboxane A2, but the cardiac release of these prostanoids has been reported infrequently. Fifty-four patients undergoing elective coronary artery bypass had coronary sinus catheters inserted to evaluate the cardiac release of the stable metabolites of prostacyclin (6-keto-prostaglandin F1 alpha) and thromboxane A2 (thromboxane B2). Arterial concentrations of 6-keto-prostaglandin F1 alpha and thromboxane B2 were elevated after cardiac cannulation and during cardiopulmonary bypass. The cardiac release of 6-keto-prostaglandin F1 alpha was observed after cannulation and during, but not after, cardiopulmonary bypass. Cardiac thromboxane B2 release was detected after cross-clamp release and persisted during the early postoperative period when cardiac 6-keto-prostaglandin F1 alpha release was no longer detectable. Cardiopulmonary bypass stimulated the systemic production of thromboxane and prostacyclin. The cardiac release of thromboxane was unopposed by cardiac prostacyclin production in the early postoperative period and may contribute to reperfusion injury.     

Thromboxane synthetase inhibition with imidazole increases blood flow in ischemic penumbra

Previous studies have indicated that the regional distribution of the arachidonic acid metabolites around a focal ischemic lesion may be important in the pathogenesis of cerebral ischemia. To determine the functional significance of this regionalization, we examined the effect of imidazole (a thromboxane synthetase inhibitor) on the distribution of the vasoconstrictor thromboxane and the vasodilators prostacyclin and prostaglandin E2 (PGE2) and on the distribution of cerebral blood flow (CBF) around a focal ischemic lesion, middle cerebral artery (MCA) occlusion in the cat. The study was conducted in two phases. The first phase examined regional distribution of tissue arachidonic acid metabolites and the effect of imidazole treatment on that distribution. The second phase examined the effect of imidazole treatment on the distribution of blood flow about the focal ischemic lesion as well as on electrocortical function and edema production. MCA occlusion resulted in increased thromboxane, prostacyclin, and PGE2 levels in the ipsilateral hemisphere. These increases were greatest in the region of marginal ischemia and were present both 3 and 6 hours after occlusion. Imidazole pretreatment (50 mg/kg i.p.) significantly inhibited thromboxane production, but augmented production of prostacyclin and PGE2. In the blood flow studies, imidazole was without effect on regions of dense cerebral ischemia (CBF less than 20 ml/minute/100 g for more than 12 of 24 postocclusion hours). In regions of marginal ischemia (20 less than CBF less than 30 ml/minute/100 g for more than 12 of 24 postocclusion hours), imidazole pretreatment significantly increased blood flow in both gray and white matter compared with saline-treated controls.(ABSTRACT TRUNCATED AT 250 WORDS)     

Early burn wound excision and skin grafting postburn trauma restores in vivo neutrophil delivery to inflammatory lesions

This study assessed the effect of early vs delayed postburn wound excision and skin grafting on the in vivo neutrophil delivery to a delayed-type hypersensitivity (DTH) reaction and a bacterial skin lesion (BSL). Male Lewis rats were presensitized to keyhole-limpet hemocyanin. Group 1 comprised sham controls. Groups 2 through 4 were given a 30% 3 degrees scald burn, but the burn wounds were excised, and skin was grafted on days 1, 3, and 7, respectively, after the burn. Group 5 comprised burn controls. Twelve days after burn trauma, all rats were injected at different intervals (during a 24-hour period) with a trio of intradermal injections of keyhole-limpet hemocyanin, Staphylococcus aureus 502A, and saline at different sites. In vivo neutrophil delivery to these dermal lesions was determined by injecting indium in 111 oxyquinoline-labeled neutrophils isolated from similarly treated groups of rats. Neutrophil delivery to DTH and BSL lesions was restored to normal by excision and skin grafting of the burn wound one day after burn trauma. Waiting three days after burn trauma to excise and skin graft the wound partially, but not completely, restored the in vivo neutrophil delivery to DTH and BSL lesions. Waiting one week to excise and skin graft a burn wound resulted in no improvement in neutrophil delivery to DTH and BSL dermal lesions. It was concluded that burn wound excision and skin grafting immediately after burn trauma restored in vivo neutrophil delivery to a BSL and DTH dermal lesion. This may, in part, explain the beneficial effect of early aggressive burn wound debridement in patients with burn injuries.     

Effect of the thromboxane synthetase inhibitor dazmegrel (UK 38,485) on skin blood flow in deep partial thickness burns

We have previously demonstrated more rapid wound healing in deep partial thickness burn guinea-pigs treated with intramuscular injection of the lower dosage of the thromboxane synthetase inhibitor Dazmegrel. In striking contrast, systemic and topical application of larger dosage of Dazmegrel inhibited or did not improve wound healing in this study, a deep partial thickness burn model of guinea-pig was used to evaluate the effect of Dazmegrel given systemically using dosage of 3.4 mg, 10 mg and 30 mg/kg/day on dermal perfusion measured by India ink injection or by Xe-133 clearance. There was no improvement of dermal perfusion in any of the groups receiving Dazmegrel. The beneficial effect of Dazmegrel on wound healing at a dosage of 3.4 mg/kg/day was not due to improved local dermal perfusion but, rather, resulted from a systemic immune effect on the animal. The Xe-133-determined blood perfusion showed a significantly diminished blood perfusion in the burn wound at 7h post-burn, and a higher burn skin blood flow at 24h post-burn. Their finding is consistent with the report from other laboratory that microvascular perfusion in zone-of-stasis burns, immediately post-burn, gradually diminishes to nil over the next 16 hours, to be followed by reperfusion between 16 and 96 hours postburn.     

Platelet-activating factor contributes to postischemic vasospasm

BACKGROUND: The purpose of the present study was to determine if platelet-activating factor is an important mediator that produces vasospasm during reperfusion after ischemia in skeletal muscle. MATERIALS AND METHODS: A vascular isolated cremaster muscle in male Sprague-Dawley rats was coupled with local intraarterial drug infusion as a model to study microcirculation responses to ischemia/reperfusion injury. Arteriole diameters and capillary perfusion were measured using intravital microscopy. Group 1: platelet-activating factor dose response. Group 2: Effects of a cyclooxygenase inhibitor; indomethacin, and a thromboxane synthetase inhibitor, imidazole, on the response to platelet-activating factor. Group 3: Effects of nitric oxide synthesis inhibitor; N(omega)-nitro-L-arginine methyl ester, on the response to platelet-activating factor. Group 4: Effects of a platelet-activating factor receptor antagonist, CV-3988, indomethacin, and imidazole after 4 h of warm ischemia and reperfusion. RESULTS: Intraarterial infusion of platelet-activating factor produced a dose-related but mild vasoconstriction. Pretreatment with indomethacin or imidazole resulted in significant vasodilation actually emanating from platelet-activating factor infusion. Nitric oxide inhibition (with N(omega)-nitro-L-arginine methyl ester) enhanced the vasoconstriction produced by platelet-activating factor. Pretreatment with CV-3988, indomethacin, or imidazole significantly attenuated ischemia/reperfusion-induced vasospasm and capillary no-reflow in the cremaster muscles. CONCLUSIONS: Ischemia/reperfusion-induced vasoconstriction is at least in part mediated by platelet-activating factor and thromboxane A(2).     

Effect of vibriolysin, an enzymatic debriding agent, on healing of partial-thickness burn wounds

Vibriolysin, a new agent for enzymatic debridement, was recently shown to rapidly and thoroughly hydrolyze burn wound eschar within full-thickness wounds. The safety of this agent and its subsequent effect on wound healing processes have yet to be established and are addressed in this study. Within the context of a porcine partial-thickness burn wound model, the enzyme was shown to digest desiccated eschar after two applications, whereas four applications of another enzymatic preparation were required. Computerized morphometric analysis of dermal and epidermal growth from histologic sections on wounds harvested at day 7 and 10 was used to assess wound healing. The data indicate that wounds treated with Vibriolysin exhibited significant dose-responsive stimulation of granulation tissue (neodermis) as compared with control treatment groups. Repeated protease applications did not convert partial-thickness burns to full-thickness wounds, and no adverse inflammatory responses were detected between 1 and 10 days. The results suggest that in addition to its documented efficacy in the debridement of burn eschar, Vibriolysin may have beneficial effects on dermal reparative events.     

Topical p38 MAPK inhibition reduces bacterial growth in an in vivo burn wound model

BACKGROUND: Although the inflammatory response is a prerequisite for wound healing, excessive activation of the innate immune system can induce epithelial cell damage and apoptosis, which may further compromise dermal integrity. In a noninfectious burn wound model, we previously demonstrated that topical inhibition of p38 MAPK, an important inflammatory signaling pathway, attenuated epithelial cell damage and apoptosis. We now question whether attenuating local inflammation would weaken bacterial wound resistance and compromise host defense. METHODS: Rats received 30% total body surface area burn, and the wound was treated with topical application of a p38 MAPK inhibitor or vehicle. At 24 hours after injury, burn wounds were inoculated with Pseudomonas aeruginosa. At 48 hours postinjury, animals were sacrificed, and the burn wound was analyzed. RESULTS: Inoculating burn wounds induced significant bacterial growth. Dermal inflammatory changes were markedly accentuated in the inoculated animals. Topical p38 MAPK inhibition reduced the proinflammatory cytokine expression in the burn wounds and neutrophil sequestration with or without bacterial inoculation. Interestingly, the bacterial wound growth was significantly attenuated in animals treated with topical p38 MAPK inhibitor. CONCLUSIONS: Topical p38 MAPK inhibition attenuated wound inflammation without interfering with bacterial host defense. Attenuation of excessive burn wound inflammatory signaling may prevent secondary damage of the dermal barrier and reduce the growth of opportunistic pathogens.