Biomedical subjects

G O Simkin

Publications and source records attributed to G O Simkin.

4 recordsLinked to original sources

PubMed2000

IL-10 contributes to the inhibition of contact hypersensitivity in mice treated with photodynamic therapy.

We have explored the effect of photodynamic therapy (PDT) with verteporfin on the induction and expression of contact hypersensitivity (CHS) to 2,4-dinitrofluorobenzene (DNFB) in normal mice and IL-10-deficient mice. Our results indicate that DNFB sensitized mice given PDT with verteporfin and whole body red light irradiation exhibited a significant reduction in CHS compared with control animals. Administration of rIL-12 reversed the effect(s) of PDT as did treatment of mice with anti-IL-10-neutralizing Ab. Knockout mice deficient in IL-10 were found to be resistant to the inhibitory effects of PDT. In vitro proliferative responses using spleen cells from DNFB-sensitized and PDT-treated mice showed a significantly lower response to DNBS as compared with cells from DNFB-sensitized mice or DNFB and PDT-treated IL-10-deficient mice. Finally, naive mice exposed to PDT exhibited an increase in skin IL-10 levels, which peaked between 72 and 120 h post-PDT. Together these data support the role of IL-10 as a key modulator in the inhibition of the CHS response by whole body PDT.

Animals↗

PubMed1999

Photodynamic alteration of the surface receptor expression pattern of murine splenic dendritic cells.

The photosensitizer benzoporphyrin-derivative monoacid ring A (BPD-MA, verteporfin), in combination with visible light irradiation, a clinical procedure termed photodynamic therapy (PDT), has immunomodulatory activity in various mouse models. We studied the impact of BPD-MA and light upon DBA/2 mouse splenic dendritic cells (DC), a potent antigen-presenting cell (APC) type. DC treated with nanomolar amounts of BPD-MA and 690 nm wavelength light had a reduced capacity to stimulate the proliferation of alloreactive T cells. Treatment with BPD-MA and light reduced DC levels of major histocompatibility (MHC) Class I and II antigens, intercellular adhesion molecule-1 (ICAM-1, CD54), the costimulatory B7-1 (CD80) and B7-2 (CD86) molecules, leucocyte common antigen CD45, the apoptosis-regulating Fas (CD95) receptor and the integrin CD11c. In contrast, DC expression of leucocyte function-associated-1 (LFA-1, CD11a), Mac-1 (CD11b), integrin beta2 chain (CD18) and the DEC-205 receptor increased, while CD40 levels were relatively unchanged 24 h after the treatment. MHC Class I and ICAM-1 levels decreased to 40% of control levels within 2 h following the photodynamic treatment. In the absence of light, BPD-MA did not affect DC receptor levels. Changes in DC receptor levels produced by BPD-MA and red light were similar to those produced by ultraviolet B light irradiation. The photodynamic treatment of activated splenic B cells, a separate APC class, had little effect upon receptor expression, except that MHC Class II levels were moderately decreased 24 h later. Changes in DC receptor expression may contribute to the immunomodulatory action of PDT.

Animals↗

PubMed1997

Inhibition of contact hypersensitivity with different analogs of benzoporphyrin derivative.

Four structural analogs of benzoporphyrin derivative (BPD), a potent anti-tumor photosensitizer, were evaluated for their capacity to influence the immunologically-mediated contact hypersensitivity (CHS) response against the hapten 2,4-dinitrofluorobenzene (DNFB). Immunocompetent hairless strain mice received BPD monoacid ring A (BPD-MA, verteporfin) and returned to normal housing conditions or treated with 690 nm red light (transcutaneous photodynamic therapy, PDT). Unexpectedly, we found that mice given BPD-MA exhibited significantly reduced CHS ear swelling responses to DNFB upon antigenic challenge, whether or not they had been treated with PDT. A significant reduction in the CHS response to DNFB was observed when BPD-MA or PDT was given 48 or 24 h prior to, on the same day, or 24 or 72 h after DNFB sensitization. However, the magnitude of the CHS response was unaffected if these treatments were given 96 h after DNFB sensitization, 24 h before challenge with DNFB. Significantly reduced CHS responses also occurred in Balb/c mice given BPD-MA with or without PDT. Mice given BPD-MA but retained in total darkness throughout the experimental period generated full-fledged ear swelling responses to DNFB indicating that CHS suppression with BPD-MA was light dependent. BPD monoacid ring B (BPD-MB) strongly reduced the CHS response of Balb/c mice kept under ambient light while BPD diacid ring A (BPD-DA) and BPD diacid ring B (BPD-DB) also lowered the CHS response but were less effective than the monoacid forms. Other photosensitizers including Photofrin, tin etiopurpurin, and zinc phthalocyanine did not alter the CHS response of Balb/c mice maintained under ambient light. The ability of different BPD analogs to inhibit the CHS response in mice held under ambient light conditions appears related to the potent photosensitizing activity of these compounds.

Adjuvants, Immunologic↗

PubMed1985

Hereditary angioedema: polymorphism.

Four patients with hereditary angioedema were studied. All had low values of C4, C1 INH, (CH 50) complement activity and circulating immune complexes. This report takes into account the different aspects that this disease can present, often quite different from the classical description of hereditary angioedema.

Adolescent↗