Phytotherapeutic approaches to common dermatologic conditions.

In this review, we discuss some common herbal preparations historically used for dermatologic conditions and recent studies that support their use. The traditional practice of topically treating dermatologic conditions with plant-derived medicines predates the cultures of ancient Egypt and remains vital today in the industrialized cultures of both the United States and Europe. Recent scientific studies lend support to some of the claims of herbal practitioners for the safety and efficacy of many herbs. The studies also elucidate, in some cases, the mechanisms by which these herbs act. With the growing interest in alternative and complementary therapies, practitioners need more information. Clinical studies and collected observations will help define specific indications for choice of herbal treatment based on both the skin disorder and the unique characteristics of the patient involved.

Specific and nonspecific immunoregulatory events in the clonal response of human lymphocytes in vitro.

Stimulation of sensitive leucocyte populations with near optimal concentrations of soluble microbial antigens results in vigorous lymphocyte proliferation when 3H-thymidine incorporation is measured after 4-8 days. Lymphoblasts in these cultures revert to small lymphocytes after 10-14 days, at which time they are often refractory to any stimulant including the original incubating antigen. When these primed lymphocytes are irradiated with 500-1000 R to block their proliferation and added to fresh leucocyte culture from the same individual (autologous), they usually, but not invariably, reduce the proliferation of the unirradiated fresh leucocyte cultures. Exposure to 6000 R reduced the suppressor activity. Reduction was specific for the microbial antigen with which they were originally generated, but, more often, a combination of both specific and nonspecific suppression was observed. These data provide good evidence, with reciprocal specificity, for the generation of antigen specific suppression in vitro.

Studies on the contact sensitization of man with simple chemicals: V. Clonal priming allows direct in vitro assessment of autologous HLA-associated factors required for immune response to dinitrochlorobenzene.

Human lymphocytes from dinitrochlorobenzene (DNCB)-sensitized human subjects primed in first culture with dinitrophenylated-antigens yield a population of cells which respond in an accelerated manner to the same or similar antigen in second culture. Using this "clonal priming" approach, we have demonstrated that such a primed population showed maximal proliferative response to dinitrophenylated autologous cells. These DNP primed clones also showed responses to some dinitrophenylated allogeneic leukocytes. The magnitude of the accelerated blastogenic response with allogeneic leukocytes varied in most instances in relation to the degree of sharing of HLA-A, B, and DRw antigens with the original autologous stimulator. These findings show that the self-specific factors recognized in conjunction with the dinitrophenyl antigen are closely but not invariably associated with established major histocompatibility (MHC)-associated serologic typing results. While DNP primed clones fail to respond to unmodified autologous leukocytes, they often show significant responses to unmodified allogeneic leukocytes. If such accelerated responses to unmodified allogeneic leukocytes are not the result of nonspecific activation of allogeneic responding lymphocyte clones, these findings further indicate that DNP modified self can resemble some alloantigens.

Selective defects in T cell function in ataxia-telangiectasia.

We have studied three patients with ataxia-telangiectasia (AT) and found two of them to have a normal mixed leucocyte culture stimulating and responding ability. However, all three patients and one parent had defective cell-mediated lympholysis (CML), even in the face of a potent proliferative response to allogeneic leucocytes. None of these patients showed significant proliferative responses to common microbial antigens (tetanus toxoid, Candida albicans, purified protein derivative (PPD), diphtheria toxoid, influenza). Our studies indicate tha the T cell defect in AT preferentially affects certain T cell functions associated with antigen recognition and the generation of allogeneic CML, while sparing the allogeneic proliferative response. The selective deficiency of specific lymphocyte functions in a thymic immunodeficiency with a known defect in DNA repair is consistent with the concept that DNA modulating enzymes are important for T cell function.

Specificity of human cytotoxic responses to chemically modified autologous cells.

Human PBML can generate cytotoxic responses to autologous cells that have been chemically modified with TNP or DNP. The cytotoxic effectors have precise hapten specificity. The DNP-specific effectors recognize DNP in association with cell surface alloantigens, which appear to be at least partially associated with HLA-A and -B. The TNP-specific effectors recognize TNP in association with several classes of determinants--some of which are HLA-linked alloantigens that are incompletely associated with HLA-A and -B, while other determinants are widely shared among humans.

Clonal priming of human lymphocytes with soluble microbial antigens: high-dose paralysis, restoration, and autologous leukocyte preference.

Lymphocytes stimulated in appropriate leukocyte cultures undergo blastogenesis and proliferation for a finite period of time. With specific antigens the proliferative response peaks usually between 4 and 8 days, after which the blastoid cells revert to small lymphocytes. Lymphocytes "primed" in this manner can be restimulated to proliferate only by the same antigen with which they were incubated and only with an adequate amount of a self-specific, autologous, somatic product(s). First or "primary" leukocyte cultures stimulated by optimal or supraoptimal concentrations of soluble protein antigens (purified protein derivative (PPD), tetanus toxoid, Candida albicans) will undergo proliferation in the first culture, but the increased number of small lymphocytes that can be visualized after 10--14 days often fail to respond to any stimulus in second (secondary) or "primed" cultures. However, when fresh X-irradiated autologous cells are re-added in appropriate amounts, vigorous accelerated proliferation takes place. Addition of allogeneic cells to antigen-primed populations has one of three effects: (1) no effect (complete restriction); (2) in some instances allogeneic cells restore a significant response to the specific antigen but almost never to the same degree as autologous cells; and (3) allogeneic cells can also induce high levels of accelerated responsiveness without added antigen. These findings are discussed in the context of a working hypothesis that self-specific factors are involved in all specific immune responses. The combination of antigen and self-specific factors may lead to a quantitatively unique immune response to all antigens in each individual. The preferential response to antigen in conjunction with autologous rather than allogeneic leukocytes suggests that self-specific products are required for recognition of soluble microbial antigens.

The effect of thymosin on human T-cells from cancer patients.

The effect of thymosin on in vitro reactivity of peripheral lymphocytes to phytohemagglutinin, concanavalin A, and the formation of spontaneous E-rosettes in 54 patients with metastatic carcinomas has been studied. Thymosin increased lymphocyte responses to PHA and Con A in only 10 patients, with predominant effect seen with Con A. Twenty patients showed depressed baseline levels of E-rosettes which were increased to normal or subnormal levels after incubation with thymosin. No distinct correlation was noted between the clinical stage of the disease and the ability of lymphocytes to form E-rosettes. Although the exact mechanism by which the thymus exerts its influence on host resistance is not clearly defined, present evidence supports the concept that the thymic hormone, thymosin, may be an important addition in treatment of cancer patients by increasing cell-mediated immunity.