Mark R. Wakefield

The paradoxical role of IL-10 in immunity and cancer

Interleukin-10 (IL-10) produced by a wide-variety of cells is a highly pleiotropic cytokine. It has been implicated in the pathogenesis and/or development of autoimmune diseases and cancer, although it displays differential effects that seem to be contradictory sometimes. The ultimate role of this cytokine in disease, however, cannot be fully determined until the immunological contexts that regulate its function are further elucidated. In this review, we will discuss a wide variety of evidence of IL-10 in immunity and cancer in an effort to illuminate the remaining mysteries in the function of this cytokine that, when fully understood, may prove to be a powerful tool in the battle against cancer.

Taking immunosuppressive medications effectively (TIMELink): a pilot randomized controlled trial in adult kidney transplant recipients.

Russell C, Conn V, Ashbaugh C, Madsen R, Wakefield M, Webb A, Coffey D, Peace L. Taking immunosuppressive medications effectively (TIMELink): a pilot randomized controlled trial in adult kidney transplant recipients. 
Clin Transplant 2011: 25: 864–870.

The role of IL-11 in immunity and cancer

Interleukin-11 (IL-11) is a member of the glycoprotein-130 (GP-130) cytokines that utilizes the GP-130 signaling pathway shared by other cytokines of the same family. Traditionally regarded as an anti-inflammatory cytokine, IL-11 also demonstrates its role as a proinflammatory cytokine, suggesting its complex role in immune response. In recent years, IL-11 has an emerging role in various inflammation-associated cancers. In this review, we aim to discuss IL-11 signaling pathway, to explore the role of IL-11 in immunity and various cancers, and to provide a therapeutic perspective of strategies utilized to interfere IL-11 signaling in cancer cells.

Medication Adherence in Older Renal Transplant Recipients

This project examined patterns, predictors, and outcomes of medication adherence in a convenience sample of 37 renal transplant recipients aged 55 years or older in a Mid-Southern U.S. facility using an exploratory, descriptive, longitudinal design. Electronic monitoring was conducted for 12 months using the Medication Event Monitoring System. An alarming 86% of the participants were nonadherent with medications. Four clusters of medication taking and timing patterns were identified with evening doses presenting particular challenges. Depression, self-efficacy, social support, and medication side effects did not predict medication adherence. There was no significant difference in medication adherence scores between those with and without infections. Medication adherence pattern data from electronic monitoring provides an opportunity for health care professionals to move away from blaming the patient by attempting to identify predictors for medication nonadherence. Medication dose taking and timing patterns could be explored with patients so that medication adherence interventions could target specific patient patterns.

Long‐Term Survival of Kidneys Transplanted from Live A2 Donors to O and B Recipients

The long‐term outcome of kidneys transplanted from blood group A2 live donors into blood group O or B candidates is not known. From 1986 through 2006, we transplanted eight blood group O patients and one blood group B patient with kidneys from blood group A2 live donors. Immunosuppression was no different for these patients than for ABO‐compatible recipients. All patients received methylprednisolone, cyclosporine or tacrolimus and azathioprine or mycophenolate mofetil with or without antibody induction (monoclonal or polyclonal). Of the nine live‐donor A2 to O and B transplants performed, seven grafts remain functioning. One of those seven was lost to follow‐up at 9.2 years with a functioning kidney. Of the remaining six patients, length of follow‐up is 10.4, 6.5, 5.3, 4, 2.1 and 1 years. Of the two patients who lost their grafts, one died with a functioning graft (DWFG) at 8.8 years and one lost his graft at 13.2 years due to noncompliance with immunosuppression. These data show that good long‐term graft survival can be expected in live‐donor A2 to O and B transplantation despite some of those patients experiencing the type of clinical problems seen with ABO‐compatible transplants.

Renal graft survival is not influenced by a positive flow B‐cell crossmatch

Abstract:  Introduction:  The influence of a positive B‐cell crossmatch on graft outcome in renal transplantation is controversial.

Sharing kidneys across donor-service area boundaries with sensitized candidates can be influenced by HLA C

Bryan CF, Luger AM, Smith JL, Warady BA, Wakefield M, Schadde E, Murillo D, Nelson PW. Sharing kidneys across donor‐service area boundaries with sensitized candidates can be influenced by HLA C.
Clin Transplant 2010: 24: 56–61.

Time‐in‐a‐bottle (TIAB): a longitudinal, correlational study of patterns, potential predictors, and outcomes of immunosuppressive medication adherence in adult kidney transplant recipients

This study examined patterns, potential predictors, and outcomes of immunosuppressive medication adherence in a convenience sample of 121 kidney transplant recipients aged 21 yr or older from three kidney transplant centers using a theory‐based, descriptive, correlational, longitudinal design. Electronic monitoring was conducted for 12 months using electronic monitoring. Participants were persistent in taking their immunosuppressive medications, but execution, which includes both taking and timing, was poor. Older age was the only demographic variable associated with medication adherence (r = 0.25; p = 0.005). Of the potential predictors examined, only medication self‐efficacy was associated with medication non‐adherence, explaining about 9% of the variance (r = 0.31, p = 0.0006). The few poor outcomes that occurred were not significantly associated with medication non‐adherence, although the small number of poor outcomes may have limited our ability to detect a link. Future research should test fully powered, theory‐based, experimental interventions that include a medication self‐efficacy component.

The role of IL-37 in cancer.

Interleukin 37 (IL-37) is a new member of the IL-1 family which all have a similar β-barrel structure. Since its discovery, IL-37 has been studied extensively in immunological field. It has been established that IL-37 possesses anti-inflammatory characteristics both in innate immune response as well as in acquired immune responses by downregulating pro-inflammatory molecules. This review will discuss the role of IL-37 in immunological processes and neoplastic pathogenesis.

Trichomonas vaginalis: a possible foe to prostate cancer.

Prostate cancer (PCA) is the most common malignancy in men in USA, and the role of Trichomonas vaginalis (T. vag) in the development of PCA is still controversial. Clonogenic assay, PCNA staining, TUNEL staining and caspase-3 activity assay were used to investigate the in vitro role of T. vag in human prostate cancer. We further investigated the possible molecular mechanisms using RT-PCR and immunohistochemical staining. Culture supernatant of T. vag inhibits growth of PC-3 prostate cancer cells, and this correlated with upregulation of p21. Culture supernatant of T. vag induced apoptosis of PC-3 cells, and this correlated with downregulation of Bcl-2. The growth inhibition effect of culture supernatant of T. vag is also demonstrated in another prostate cancer cell line DU145, suggesting that its effect is not specific to one prostate cancer cell line. Culture supernatant of T. vag inhibits growth of prostate cancer by inhibition of proliferation and promotion of apoptosis. Such a study might be helpful to address the association between PCA and infection of T. vag.