Ultraviolet Irradiation of Blood: ‘The Cure That Time Forgot’?

Abstract: Ultraviolet blood irradiation (UBI) was extensively used in the 1940s and 1950s to treat many diseases including septicemia, pneumonia, tuberculosis, arthritis, asthma and even poliomyelitis.

25.1. Historical Introduction

Ultraviolet (UV) radiation is part of the electromagnetic spectrum with a wavelength range (100–400 nm) shorter than that of visible light (400–700 nm), but longer than x-rays (<100 nm). UV radiation is divided into four distinct spectral areas including vacuum UV (100–200 nm), UVC (200–280 nm), UVB (280–315 nm) and UVA (315–400 nm). Only part of UVB and UVA can reach on earth, because wavelengths shorter than 280 nm are filtered out by the atmosphere especially by the “ozone layer”.

In 1801 Johann Wilhelm Ritter, a Polish physicist working at the University of Jena in Germany discovered a form of light beyond the violet end of the spectrum that he called “Chemical Rays” and which later became “Ultraviolet” light [1]. In 1845, Bonnet [2] first reported that sunlight could be used to treat tuberculosis arthritis (a bacterial infection of the joints).

In the second half of the nineteenth century, the therapeutic application of sunlight known as heliotherapy gradually became popular. In 1855, Rikli from Switzerland opened a thermal station in Veldes in Slovenia for the provision of helio-therapy [3]. In 1877, Downes and Blunt discovered by chance that sunlight could kill bacteria [4]. They noted that sugar water placed on a window- sill turned cloudy in the shade but remained clear while in the sun. Upon microscopic examination of the two solutions, they realized that bacteria were growing in the shaded solution but not in the one exposed to sunlight.

In 1904, the Danish physician Niels Finsen was awarded the Nobel Prize in Physiology or Medicine for his work on UV treatment of various skin conditions. He had a success rate of 98{154653b9ea5f83bbbf00f55de12e21cba2da5b4b158a426ee0e27ae0c1b44117} in thousands of cases, mostly the form of cutaneous tuberculosis known as lupus vulgaris [5]. Walter H Ude reported a series of 100 cases of erysipelas (a cutaneous infection caused by Streptococcus pyogenes) in the 1920s, with high cure rates using irradiation of the skin with UV light [6].

Emmett K Knott (Fig. 25.1) in Seattle, WA reasoned that the beneficial effects of UV irradiation to the skin obtained by Ude, might (at least partly) be explained by the irradiation of blood circulating in the superficial capillaries of the skin. With his collaborator Edblom, an irradiation chamber was constructed to allow direct exposure of the blood to UV.

The irradiation chamber was circular and contained a labyrinthine set of channels that connected the inlet and outlet ports. All these channels were covered with a quartz window that formed the top of the chamber. The irradiation chamber was so designed as to provide maximum turbulence of the blood flowing through (see Fig. 25.2).

This was done in order to: (a) prevent the formation of a thin film of blood on the chamber window that would absorb and filter out much of the UV light; (b) insure that all the blood passing through the chamber was equally exposed to UV [7].

Knott and co-workers then carried out a series of experiments using UV irradiation of blood extracted from dogs that had been intravenously infected with Staphylococcus aureus bacteria and hemolytic Streptococcus species, and then the treated blood was reinfused into the dogs. They found that it was unnecessary to deliver a sufficient exposure of UV light to the blood to directory kill all the bacteria in the circulation.

It was also found unnecessary to expose the total blood volume in the dogs. The optimum amount of blood to be irradiated was determined to be only 5–7{154653b9ea5f83bbbf00f55de12e21cba2da5b4b158a426ee0e27ae0c1b44117} of the estimated blood volume or approximately 3.5 mL per kg of body weight. Exceeding these limits led to loss of the benefits of the therapy.

All the dogs that were treated with the optimized dose of UV to the blood, recovered from an overwhelming infection (while many dogs in the control group died). None of the dogs that were treated and survived, showed any long-term ill effects after 4 months of observation [7].

The first treatment on a human took place in 1928 when a patient was determined to be in a moribund state after a septic abortion complicated by hemolytic streptococcus septicemia. UBI therapy was commenced as a last resort, and the patient responded well to the treatment and made a full recovery [7]. She proceeded to give birth to two children.

Hancock and Knott [8] had similar success in another patient suffering from advanced hemolytic streptococcal septicemia. These workers noted that in the majority of cases, a marked cyanosis (blue tinge to the skin caused by a lack of oxygenated blood flow) was present at the time of initiation of UBI. It was noted that during (or immediately following) the treatment a rapid relief of the cyanosis occurred, with improvement in respiration accompanied by a noticeable flushing of the skin, with a distinct loss of pallor.

These observations led to application of UBI in patients suffering from pneumonia. In a series of 75 cases in which the diagnoses of pneumonia were confirmed by X-rays, all patients responded well to UBI showing a rapid decrease in temperature, disappearance of cyanosis (often within 3–5 min), cessation of delirium if present, a marked reduction in pulse rate and a rapid resolution of pulmonary consolidation. A shortening of the time of hospitalizations and accelerated convalescence was regularly observed.

The knowledge gained in these successful studies led to the redesign of the irradiation chamber to allow a more thoroughly uniform exposure of the circulating blood, and led to the development of the “Knott Technic of Ultraviolet Blood Irradiation.” A number of irradiation units were manufactured and placed in the hands of physicians interested in the procedure, so that more extensive clinical data could be accumulated [7].

The Knott technique involved removing approximately 3.5 mL/kg venous blood, citrating it as an anticoagulant, and passing it through the radiation chamber. The exposure time per given unit of blood was approximately 10 s, at a peak wavelength of 253.7 nm (ultraviolet C) provided by a mercury quartz burner, and the blood was immediately re-perfused [7].

George P Miley at the Hahnemann Hospital, Philadelphia, PA published a series of articles on the use of the procedure in the treatment of thrombophlebitis, staphylococcal septicemia, peritonitis, botulism, poliomyelitis, non-healing wounds, and asthma [9–22].

Henry A Barrett at the Willard Parker Hospital in New York City in 1940 reported on 110 cases including a number of different infections. Twenty-nine different conditions were described as being responsive, including the following: infectious arthritis, septic abortion, osteoarthritis, tuberculosis glands, chronic blepharitis, mastoiditis, uveitis, furunculosis, chronic paranasal sinusitis, acne vulgaris, and secondary anemia [23, 24].

EV Rebbeck at the Shadyside Hospital in Pittsburgh, PA, reported the use of UBI in Escherichia coli septicemia, post-abortion sepsis, puerperal sepsis, peritonitis, and typhoid fever [25–29] and Robert C Olney at the Providence Hospital, Lincoln, NE, treated biliary disease, pelvic cellulitis and viral hepatitis [30–32].

In this chapter, we will discuss the mechanisms and the potential of UBI as an alternative approach to infections and as a new method to modulate the immune system. Our goal is to remind people to continue to do more research and explore more clinical uses. The topics include the efficacy of UBI for infections (both bacterial and viral), to cure autoimmune disease, disease, and the similarities and differences between UBI, and intravenous ozone therapy, and extracorporeal psoralen-mediated photochemotherapy (photophoresis).

25.2. Mechanisms of Action of UBI

One of the major obstacles that UBI has consistently faced throughout the almost 90 years since the first patient was treated has been the lack of understanding of the mechanisms of action. Over the years its acceptance by the broad medical community has been hindered by this uncertainty.

Confusion has been caused by the widely held idea that since UV is used for sterilization of water and surgical instruments; therefore its use against infection must also rely on UV-mediated direct destruction of pathogens. Another highly confusing aspect is the wide assortment of diseases, which have been claimed to be successfully treated by UBI. It is often thought that something that appears to be “too good to be true” usually is.

UBI affects various functions of red blood cells and various different leukocytes as has been proven in various in vitro studies. A common model is stimulator cells in mixed leukocyte cultures; another is helper cells in mitogen- stimulated cultures. UV also reversed cytokine production and blocked cytokine release. UV can also disturb cell membrane mobilization (Fig. 25.3).

25.2.1. Effects on Red Blood Cells

Anaerobic conditions strongly inhibited the process by which long wave UV light induces the loss of K⁺ ions from red blood cells. Kabat proved that UV-irradiation could affect the osmotic properties of red blood cells, the submicroscopic structure and the metabolism of adenine nucleotides.

Irradiation times (60, 120, 180, 240 and 300 minutes) were used; during the irradiation, ATP decreased while the amounts of ADP, AXP, adenine compounds all increased. UV also increased hypotonic Na + and K+ ion exchange and the hematocrit value increased [33].

When Rh-positive blood was irradiated with UV light there was a significant increase in immunosorption activity. Vasil’eva et al. [34] studied varying UV irradiation conditions on both red blood cells and leucocyte-thrombocyte suspensions. Immunosorption activity increased immediately after irradiation in whole blood and red blood cells; however the immunosorption capacity in leucocyte–thrombocyte suspensions was lost after 2 days.

A two-phase polymer system containing poly-dextran was used to show that the cell surface of circulating erythrocytes was reduced after UV irradiation. This contributed to the prolongation of survival of transfused erythrocytes and was suggested to explain the more effective therapeutic activity of autotransfused blood [35].

Snopov et al. suggested that some structural alterations in the erythrocytes, particularly in the glycocalyx were related to the improved effect of autotrans-fused blood after UV-irradiation [36]. Ichiki et al. showed that the cellular volume and the membrane potential of erythrocytes could be changed by UV irradiation. However an excessive dose of UV could decrease the production of H₂O₂ [37].

Read the full paper at www.ncbi.nlm.nih.gov

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