Edward Lahey

Selective Suppression of IL-12 Production by Chemoattractants

We investigated the ability of chemoattractants to affect IL-12 production by human monocytes and dendritic cells. We found that pretreatment of monocytes with macrophage chemoattractant proteins (MCP-1 to -4), or C5a, but not stromal-derived factor-1, macrophage inflammatory protein-1α, RANTES, or eotaxin, inhibited IL-12 p70 production in response to stimulation with Staphylococcus aureus, Cowan strain 1 (SAC), and IFN-γ. The production of TNF-α and IL-10, however, was minimally affected by any of the chemoattractants. The degree of inhibition of IL-12 p70 production by MCP-1 to -4 was donor dependent and was affected by the autocrine inhibitory effects of IL-10. In contrast, C5a profoundly suppressed IL-12 production in an IL-10-independent fashion. Neither TGF-β1 nor PGE2 was important for the suppression of IL-12 by any of the chemoattractants tested. The accumulation of mRNA for both IL-12 p35 and p40 genes was inhibited by chemokine pretreatment. Interestingly, MCP-1 to -4 and C5a did not suppress IL-12 production by monocyte-derived dendritic cells (DC) stimulated with CD40 ligand and IFN-γ or by SAC and IFN-γ, suggesting that these factors may act at the site of inflammation to suppress IL-12 and IFN-γ production rather than in the lymph node to affect T cell priming. Despite the inability of C5a to inhibit IL-12 production by DCs, the receptor for C5a (CD88) was expressed by these cells, and recombinant C5a induced a Ca2+ flux. Taken together, these results define a range of chemoattractant molecules with the ability to suppress IL-12 production by human monocytes and have broad implications for the regulation of immune responses in vivo.

Antibodies to Complement Receptor 3 Treat Established Inflammation in Murine Models of Colitis and a Novel Model of Psoriasiform Dermatitis

Prior studies indicated the ability of Abs to complement receptor 3 (CR3, CD11b/CD18) to suppress the production of IL-12 from immune cells. Therefore, we tested the ability of an anti-CR3 Ab (clone M1/70) to treat established IL-12-dependent Th1-mediated inflammation in murine models. Systemic administration of anti-CR3 significantly ameliorated established intestinal inflammation following the intrarectal administration of trinitrobenzene sulfonic acid (TNBS-colitis), as well as colitis and skin inflammation in C57BL/10 RAG-2−/− mice reconstituted with CD4+CD45RBhigh T cells. The hyperproliferative skin inflammation in this novel murine model demonstrated many characteristics of human psoriasis, and was prevented by the adoptive transfer of CD45RBlow T cells. In vitro and in vivo studies suggest that anti-CR3 treatment may act, at least in part, by directly inhibiting IL-12 production by APCs. Administration of anti-CR3 may be a useful therapeutic approach to consider for the treatment of inflammatory bowel disease and psoriasis in humans.

Floor-of-Mouth Dermoid Cysts: Report of 3 Variants and a Suggested Change in Terminology

PURPOSE Dermoid cyst is a frequently used descriptive term, but its definition changes according to the clinician (eg, dermatologists, neurologists, gynecologists, oral and maxillofacial surgeons, and plastic surgeons). It is sometimes used synonymously with teratoma. In oral and maxillofacial surgery, it is applied to describe congenital floor-of-mouth cysts of 3 histologic types: epidermoid, dermoid, and teratoid. This terminology is confusing and has led to some ambiguity in the literature. The purpose of this report is to document 3 cases illustrating the utility of a more specific term, congenital germline fusion cyst of the floor of the mouth. PATIENTS AND METHODS Patients who presented with floor-of-mouth swelling were evaluated by history, clinical examination, and imaging studies (magnetic resonance imaging and computed tomography). RESULTS Three cases (1 epidermoid variant, 1 dermoid variant, and 1 teratoid variant) are documented to illustrate the new terminology. CONCLUSION Congenital germline fusion cyst is more reflective of the embryologic origins of the lesion than dermoid cyst and is inclusive of all 3 histologic variants.

Extranodal Natural Killer T-Cell Lymphoma, Nasal Type, With Minimal Osseous Involvement: Report of a Case and Literature Review

Extranodal natural killer/T-cell lymphoma (ENKTCL) is a rare form of Epstein-Barr virus (EBV)-associated non-Hodgkin lymphoma (NHL). 1-4 The nose and para-nasal sinuses are the most commonly reported sites of initial involvement. ENKTCL is reported most frequently in East Asian populations and is notably rare in Western populations. The purposes of this case report are to describe an atypical presentation of ENKTCL involving primarily the soft tissues of the midface and to highlight the vigilance required in diagnosing this cause of nonresolving facial swelling.

Periarticular Cysts of the Temporomandibular Joint Are More Frequently Synovial Than Ganglion

PURPOSE Differentiating between ganglion and synovial cysts by standard histology is difficult, leading to inaccurate statements on frequency for each of these periarticular lesions. The purpose of this study was to use immunohistochemical (IHC) analysis to 1) calculate the accuracy of the histologic diagnoses, 2) determine the frequency of ganglion and synovial cysts of the temporomandibular joint (TMJ), and 3) compare the frequency of these lesions in the TMJ compared with the extracranial skeleton in patients treated at Massachusetts General Hospital (MGH). MATERIALS AND METHODS This is a retrospective cohort study of all patients undergoing treatment of TMJ cysts at MGH from 2001 through 2013. IHC analysis of tissue samples for each patient was completed and compared with the original histologic diagnoses. Categorical variables, including age, gender, and sidedness, were recorded. A natural language search of the MGH Department of Pathology database determined the frequency of extracranial periarticular cysts during the same period. RESULTS Thirteen patients met the inclusion criteria. Eleven cysts were synovial and 2 were ganglion based on histology. IHC analysis identified 2 false-positive synovial cyst diagnoses, resulting in 100% sensitivity and 50% specificity for the original histologic assessment and a percentage error of 22%. Of the periarticular TMJ lesions, 69% were synovial cysts and 31% were ganglion cysts. The frequency of TMJ versus extracranial ganglion cysts was 0.24%, and the frequency of TMJ versus extracranial synovial cysts was 0.60% based on 3,176 extracranial cysts (1,506 synovial; 1,670 ganglion). CONCLUSION This study represents the largest single-institution experience with periarticular cysts of the TMJ, and contrary to previous reports, TMJ cysts appear to be more frequently synovial than ganglion. IHC can be used to overcome the relatively poor specificity of histologic diagnosis of synovial cysts.

Rhabdomyolysis After Prolonged Surgery: Report of 2 Cases and Review of Literature

Rhabdomyolysis is a condition in which damaged muscle tissue breaks down and intracellular contents, including myoglobin, are released into the circulation. This produces a nonspecific clinical syndrome including electrolyte disturbances, hypovolemia, metabolic acidosis, coagulopathies, and risk of acute kidney injury. Rhabdomyolysis has been reported as a complication of prolonged surgical procedures but has rarely been reported in the oral and maxillofacial surgery literature. Early diagnosis and treatment of rhabdomyolysis are important to avoid long-term complications such as renal failure. We present 2 cases of postoperative rhabdomyolysis after prolonged maxillofacial surgical procedures in which the patients were managed without long-term sequelae. The pathophysiology, risk factors, diagnosis, and treatment of postoperative rhabdomyolysis are discussed, with a brief review of the literature.