Wanda Brajczewska-Fisher MD, PhD, specialist in dermatology and immunology

At the present time, while considering the physiologic processes taking place within healthy skin and skin diseases, one should apply so called “intelligent cosmetology”, which is based on molecular biology and takes into account the role of immunological phenomena. Maintaining proper immunity of the skin tissue depends on the effective cooperation between the bone marrow derived lymphoid cells residing there. There are for example: granulocytes, monocytes, macrophages and lymphocytes, which are the so called T lymphocytes – thymus dependent and thymus-maturing lymphocytes (thymus being the central lymphoid organ) as well as thymus independent, or so called B lymphocytes, which differentiate under the influence of the lymphoid tissue of the digestive tract.

If working efficiently, cells of the immune system can destroy pathogenic substances directly (known as local cytotoxicity) or indirectly by producing inactivating proteins – antibodies.

Successful defence in the skin tissue can be attained only if the following conditions are met: a key role is taken by the T lymphocytes and so called memory cells are produced for the pathogens encountered, moreover, if there is effective cooperation between helper T lymphocytes and B lymphocytes in the process of antibody production. The function of suppressor T lymphocytes is also important, as they play an essential role in immunosurveillance.

During cell cooperation, intercellular signals called cytokines (which are substances of low molecular weight) are sent. This name is applied to a wide range of proteins: cellular growth factors, interleukins, monokines and chemokines. Cytokines promote cell proliferation and maturation, the migration of cells to infected areas, the destruction of malignant cells as well as the production of various substances (including other cytokines and collagen).

From a cosmetology perspective, cytokines are present in the skin and worthy of note as they carry out a protective function including: renewal of the epidermis, collagen synthesis and a reconstructive process related to the length of the skin’s degeneration.

The most important skin cytokines are produced by keratinocytes – live cells of the stratum basale. They promote or inhibit the activity of fibroblasts (cells produced in the tissues as a result of transformation from macrophages) as well as the skin’s vascular endothelial cells and pigment cells (melanocytes).

The following cytokines stimulate fibroblast reproduction and the production of collagen:

  • FGF (Fibroblast Growth Factor) – fibroblast growth factor produced by keratinocytes, it stimulates the maturation of fibroblasts and the production of collagen – creating a skin supporting substance,
  • TGF (Transforming Growth Factor) – a group of growth factors which transform cells while at the same time stimulating angiogenesis (the formation of new blood vessels in the skin, through its influence on the vascular endothelial cells) also produced by keratinocytes in the epidermis cells.

The following cells may also produce substances promoting fibroblast growth

  • PDGF (Platelet-Derived Growth Factor) – it is a factor regulating growth and maturation of platelets; it promotes fibroblast proliferation and production of collagen during inflammation processes – it is secreted by platelets.
  • IL 1 (Interleukin 1) is produced by blood monocytes and skin macrophages, it is called proinflammatory cytokine. It intensifies the skin’s inflammation processes while at the same time activating fibroblasts at a high level.
  • IL 6 (Interleukin 6) is produced by, among others, fibroblasts and macrophages. Interleukin 6 stimulates fibroblast growth and intensifies collagen production; it belongs to the group of cytokines intensifying inflammation reactions.

In some conditions, where Interleukin 6 takes a form connected with serum proteins inhibiting its function, it inhibits fibroblast proliferation and the production of collagen. Adding type IV and V collagen to a skin cell culture inhibits the function of fibroblast growth factor, also responsible for increased growth of new vessels.

Fibroblasts themselves also produce and secrete such cytokines as epidermis cell growth factor (Interleukin 6) thus regulating the maturation and proliferation of fibroblasts and the production of collagen.

The above described functional interdependence of epidermis cells, lymphoid cells and fibroblasts, intermediated by informative protein substances (cytokines) forms a rough presentation of a complicated network of interconnections resulting in the undisturbed physiological production of collagen by the fibroblasts of the skin.

The balance between creating (production) and decomposition (destruction) of collagen is disturbed as a result of skin aging and some forms of dermatosis. The decomposition of collagen and elastin structures, which progresses with age, lowers the value of the support structure of the dermis-epidermis line and in the dermis, while also lowering the permeability of the blood vascular walls feeding the dermis and hypodermis. Supplying additional doses of transdermal collagen to the skin surface in the form of well-absorbed gel has become the basis of modern non-invasive cosmetology. Regular application of collagen derived from fish skin preserves the structure of the triple helix. As a result of its filtration through silk fibroin, it is well absorbed after a few minutes, allowing a quick effect of well moisturized skin, skin elasticity and general reconstruction of the extracellular matrix of the skin. Positive effects preserved in the skin tissue include renewal of elasticity and skin tension. These can be obtained after only a few months of application and moreover, in cases of skin irritation, a clearly soothing effect can be observed.
Applying transdermal collagen accelerates the occurrence of positive cosmetic results, as opposed to local application of vitamin A derivatives (retinoids) – where positive effects were noticeable after ten months of application. Therefore it is understandable that transdermal collagen should attract growing attention.
What is more, expectations connected with the occurrence of excellent cosmetic results from preparations containing a group of cytokines derived from bovine colostrum (applied in the past few years) have fallen short.

Applying transdermal collagen to skin diseases

According to recent clinical observations, positive results can be obtained by applying collagen to various forms of allergies and diseases connected with dyskeratoses (psoriasis, follicular hyperkeratosis) and in skin diseases connected with the malfunction of the sebaceous glands (juvenile acne and acne rosacea); except for the occurrences of deep phlegmonous changes, which require anti-infectious treatment first.

In some forms of progressive psoriasis, where the intensified pathological changes cover a wide surface of the skin and are accompanied by exudate, the application of collagen may fail to bring the results expected.

Likewise, transdermal collagen is not advisable in cases of therapeutic long-term exposure to ultraviolet rays (known as phototherapy) as treatment for psoriasis received after previous sensitization of the skin to light by plant substances (psolarens). This is due to the inhibiting of cell division and a cell disintegration processes in the epidermis which takes a longer time for regeneration. Transdermal collagen application can bring excellent results in chronic vascular diseases (shank varicose veins) in which trophic changes occur, caused by dermal and hypodermal ischemia.

In other cases of dermal and hypodermal defects in collagen structure, such as congenial and acquired striae of the skin and in the irregular distribution of adipose tissue under the skin, called cellulites syndrome; a several-month, regular application of transdermal collagen gradually restores physiological conditions. Transdermal collagen applied in order to accelerate treatment of non-infected wounds appearing after skin injuries, applied on the skin around the wound, brings excellent results. Similarly, regular and long-term application of collagen on various types of post-traumatic and post-operative scars, brings an excellent cosmetic result. Should a benign hyperplasia, called a colloid, appear around the scars, collagen should be applied at three to four weeks after finishing therapy with topical agents such as 5-fluorouracil in the form of creams and ointments. These precautions must be taken due to the danger of intensifying the inflammation around the keloid while simultaneous treatment limits proliferation of malignant cells due to the application of transdermal collagen. The collagen layer applied on the keloid is most likely, to prevent change, while gradual disposal of the metabolic products from keloid cytolysis by the epidermis occurs under the therapy, leading to inhibition of cell division in the pathogens and their final destruction.

Excellent results are also obtained after application of collagen on first degree-burns of the skin.
Initiation of collagen application should, nevertheless, be delayed in burns resulting from radiotherapy of the skin or malignant neoplasm in other organs where extensive skin erythema and exfoliation of the epidermis appear. The early sharp skin reaction after radiotherapy is a side reaction by the surrounding tissues, and takes place as a result of the use of ionization.

The final target of radiation is the DNA molecules in the nucleus of the neoplastic cells and its eventual disintegration resulting directly from radiotherapy. Free radicals on the target cells may occur as a by-product. Free radicals, as unstable molecules, may also damage the DNA, intensifying destruction of the neoplastic cells. This early post-radiation reaction lasts up to 6 weeks after radiotherapy is finished. The application of transdermal collagen should start after this period, so that the skin’s integument tissues may rid themselves of cytolysis metabolites. Whereas in cases of older post-radiation scars, transdermal collagen may always be applied with satisfactory cosmetic results.

The most important problems connected with the establishing of safe and effective procedures in some of the dermatological diseases encountered by modern cosmetology were presented above. New issues connected with beneficial effects of transdermal collagen in medical cosmetology and the strategy of its application, come as a result of the constantly growing scope of new discoveries in the field of biomolecular medicine.